Benzimidazole derivatives and their uses

ABSTRACT

The present invention relates to inhibitors of Transient Receptor Potential Channel 6 (TRPC6) protein activity. The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.

The present invention relates generally to Transient Receptor PotentialCanonical (TRPC) Channel proteins, and more particularly to inhibitorsof Transient Receptor Potential Channel 6 (TRPC6) protein activity,pharmaceutical compositions comprising said inhibitors and to methods ofusing such inhibitors.

BACKGROUND OF THE INVENTION

The TRPC6 channel, a member of the Transient receptor potential (TRP)family, which is a non-selective cation-permeable channel, is activatedby diacylglycerol and the like produced by activation of phospholipase Cand exerts physiological and pathophysiological effects. TRPC6 haseffects such as cardiac pathological hypertrophy and fibrosis,progression of myocardial damage in muscular dystrophy, acute pulmonaryvasoconstriction, pathological progression in chronic hypoxia-inducedpulmonary hypertension, allergic airway response, migration of cellssuch as neutrophils, increased permeability of endothelial cells oninflammation, pathological flattening of podocytes and progression ofglomerular injury, and proliferation or infiltration of malignanttumors, and is diversely distributed in the brain, heart, lungs,kidneys, placenta, ovaries, spleen, and the like (see for example J.Clin. Invest. 116:3114-3126, 2006; Dev. Cell. 23:705-715, 2012; Circ.Res. 114:823-832, 2014; Proc. Natl. Acd. Sci. USA 103:19093-19098, 2006;J. Cardiovasc. Pharmacol. 57:140-147, 2011; Hypertension 63:173-80,2014; Clin. Exp. Allergy 38:1548-1558, 2008; Acta. Physiol. 195:3-11,2009; J. Exp. Med. 209:1953-1968, 2011; Arterioscler. Thromb. Vasc.Biol. 33:2121-2129, 2013; PLoS ONE 5: e12859, 2010; Expert. Opin. Ther.Targets. 14:513-27, 2010; and BMC Cancer 13:116, 2013). In familialfocal segmental glomerulosclerosis (FSGS), gain-of-function mutants ofTRPC6 have been identified, and in steroid resistant nephrotic syndromeor idiopathic pulmonary arterial hypertension patients, a singlenucleotide polymorphism in the promoter region that increases mRNAexpression of TRPC6 has been identified (see for example: Pediatr Res.2013 November; 74(5):511-6 and Circulation. 2009 May 5;119(17):2313-2322). Thus, it is considered that hyperfunction andincreased expression of TRPC6 contribute to pathological progression ofnephrotic syndrome, pulmonary hypertension and the like (see for exampleScience 308:1801-1804, 2005: Nat. Genet. 37:739-744, 2005; PLoS One 4:e7771, 2009; Clin. J. Am. Soc. Nephrol. 6:1139-1148, 2011; Mol. Biol.Cell. 22:1824-1835, 2011; BMC Nephrol. 14:104, 2013; Pediatr. Res.74:511-516, 2013; and Nephrol. Dial. Transplant. 28:1830-1838, 2013).Furthermore, increased expression of TRPC6 has been reported in minimalchange nephrotic syndrome, membranous nephropathy, and diabeticnephropathy (see,) for example, Circulation 119:2313-2322, 2009; J. Am.Soc. Nephrol. 18:29-36, 2007; and Nephrol. Dial. Transplant. 27:921-929,2012).

New approaches are needed to modulate TRPC6 activity and moreparticularly inhibit TRPC6 activity in the prevention and/or treatmentof nephrotic syndrome, minimal change disease, focal segmentalglomerulosclerosis, collapsing glomerulopathy, membranous nephropathy,membranoproliferative glomerulonephritis, IGA nephropathy, acute renalfailure, chronic renal failure, diabetic nephropathy, sepsis, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS) heart failure, stroke, malignant tumor, and muscular dystrophy.There remains a need for agents that exploit different mechanisms ofaction and may have better outcomes in terms of relief of symptoms,safety, and patient mortality, both short-term and long-term.

SUMMARY OF THE INVENTION

The present invention provides compounds which inhibit TRPC proteins,and more specifically inhibit TRPC6 proteins. The present inventionprovides, in one aspect, benzimidazole compounds which inhibit TRPC6activity. Inhibition of TRPC6 activity may be particularly desirable inthe treatment or prevention of a variety of diseases including nephroticsyndrome, focal segmental glomerulosclerosis, membranous nephropathy,diabetic nephropathy, heart failure, stroke, acute lung injury, acuterespiratory distress syndrome (ARDS) and acute renal failure.

The invention provides, in one aspect, substituted benzimidazolecompounds which modulate the activity of TRPC6. Preferably, thesubstituted benzimidazole compounds of the invention are TRPC6inhibitors.

The substituted benzimidazole compounds of the invention are compoundsand salts according to Formula (I):

Also provided is a pharmaceutical composition comprising apharmaceutically acceptable excipient, carrier or adjuvant and at leastone compound of Formula (I) or subformulae thereof. Pharmaceuticalcompositions provided by the invention are suitable for use in thetreatment of disease modulated by TRPC6 activity. In certain aspects thepharmaceutical compositions of the invention are suitable for use in thetreatment of, e.g., treatment of nephrotic syndrome, minimal changedisease, focal segmental glomerulosclerosis, collapsing glomerulopathy,membranous nephropathy, membranoproliferative glomerulonephritis, IGAnephropathy, acute renal failure, chronic renal failure, diabeticnephropathy, sepsis, pulmonary hypertension, acute lung disorder, heartfailure, stroke, malignant tumor or muscular dystrophy.

Also provided is a packaged pharmaceutical composition, comprising apharmaceutical composition comprising a pharmaceutically acceptableexcipient, carrier or adjuvant and at least one compound of formula (I)or subformulae thereof, and instructions for using the composition totreat a patient suffering from a disease mediated by TRPC6 activity ormore particularly to treat a patient suffering from nephrotic syndrome,minimal change disease, focal segmental glomerulosclerosis, collapsingglomerulopathy, membranous nephropathy, membranoproliferativeglomerulonephritis. IGA nephropathy, acute renal failure, chronic renalfailure, diabetic nephropathy, sepsis, pulmonary hypertension, acutelung disorder, acute respiratory distress syndrome (ARDS) heart failure,stroke, malignant tumor or muscular dystrophy. In certain instances, thepatient is suffering from nephrotic syndrome, membranous nephropathy,and acute renal failure.

Also provided is a method of treating or preventing disease in a mammalwhich method comprises administering to a mammal in need thereof atherapeutically effective amount of at least one compound of formula (I)or subformulae thereof or a pharmaceutical composition comprising apharmaceutically acceptable excipient, carrier or adjuvant and at leastone compound of formula (I) or subformulae thereof.

Also provided is a method for modulating TRPC6 activity in a mammal,which method comprises administering to the mammal in need thereof atherapeutically effective amount of at least one compound of formula (I)or subformulae thereof or a pharmaceutical composition comprising apharmaceutically acceptable excipient, carrier or adjuvant and at leastone compound of formula (I) or subformulae thereof. Another aspect ofthe invention relates to a method of treating a TRPC6-mediated diseaseor disorder, the method comprising administering a TRPC6 inhibitor ofthe invention to a patient in need of therapy. In certain embodiments,the TRPC6 mediated disease or disorder is selected from nephroticsyndrome, minimal change disease, focal segmental glomerulosclerosis,collapsing glomerulopathy, membranous nephropathy, membranoproliferativeglomerulonephritis, IGA nephropathy, acute renal failure, chronic renalfailure, diabetic nephropathy, sepsis, pulmonary hypertension, acutelung disorder, acute respiratory distress syndrome (ARDS), heartfailure, stroke, malignant tumor or muscular dystrophy. In certaininstances, the patient is suffering from nephrotic syndrome, membranousnephropathy, and acute renal failure.

Also provided is the use, in the manufacture of a medicament fortreating or preventing disease mediated by TRPC6 activity, of at leastone compound of formula I or subformulae thereof.

Other aspects and embodiments will be apparent to those skilled in theart form the following detailed description.

DETAILED DESCRIPTION OF THE INVENTION

The invention related generally to compounds of Formula I and salts andtautomers thereof which inhibit TRPC protein activity and moreparticularly inhibit TRPC6 protein activity. In particular, theinvention relates to compounds which selectively inhibit TRPC6 proteinactivity.

In a first embodiment, the invention provides a compound orpharmaceutically acceptable salt thereof, according to Formula I:

Wherein

p is 0 or 1;

when p is 0, then R¹ is hydrogen, C₁-C₆alkyl, halogen or hydroxy; R² isamino or aminoC₁-C₄alkyl; R³ is hydrogen; and R⁴ is hydrogen, C₁-C₆alkylor phenyl; or when p is 0, then R¹ and R³, taken in combination, form afused C₃-C₆cycloalkyl ring or a fused 4 to 6 member heterocycle ringhaving 1 or 2 ring heteroatoms independently selected from N, O or S,which cycloalkyl or heterocycle is optionally substituted with amino; R²is hydrogen, C₁-C₆alkyl or aminoC₁-C₄alkyl; and R⁴ is hydrogen; or

when p is 1, then R¹ is NHR^(1a); R^(1a) is hydrogen, C₁-C₄alkyl,C₃-C₇cycloalkyl, hydroxyC₁-C₄alkyl, or 4 to 6 member heterocycloalkylhaving one ring heteroatom selected from N, O or S; R² is hydrogen,C₁-C₄alkyl, hydroxyC₁-C₄alkyl or C(O)NH₂; R³ is hydrogen, halogen,C₁-C₄alkyl, C₁-C₄alkoxy or hydroxy; and R⁴ is hydrogen, C₁-C₄alkyl orhalogen; or

when p is 0 or 1, then CR¹R², taken in combination, form a spirocyclic 4to 6 member heterocycloalkyl; R³ is hydrogen, halogen. C₁-C₄alkyl,C₁-C₄alkoxy, or hydroxy; and R⁴ is hydrogen or halogen; or

when p is 1, then R¹ and R³, taken in combination, form a fused 4 to 6member heterocycle or a fused 3 to 7 member carbocycle, whichheterocycle comprises a ring nitrogen atom and optionally 0 or 1additional ring heteroatoms selected from N, O and S, and whichcarbocycle is substituted with amino; and R² is hydrogen; and R⁴ ishydrogen, halogen or hydroxy;

R⁵ represents 1 or 2 substituents independently selected from hydrogen,halogen, hydroxy, amino, C₁-C₆alkyl or C₁-C₆alkoxy;

R⁶ is —(CR⁷R⁸)-A; or

R⁶ is a 4 to 7 member lactam which is optionally substituted with one ortwo substituents independently selected from the group consisting ofhydroxy. C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, hydroxy C₁-C₆alkyl,C₁-C₆alkoxy C₁-C₆alkyl, phenyl, 4 to 7 member heterocycle having 1 ringatoms selected from N, O or S and 0 or 1 additional ring N atoms or 5 or6 member heteroaryl having one ring heteroatom selected from N, O or Sand 0 or 1 additional ring nitrogen atom, wherein the heteroaryl,heterocycle or phenyl group is optionally substituted with 0, 1 or 2C₁-C₆alkyl or halogen; or

R⁶ is a partially unsaturated 9 or 10 member bicyclic carbocycle, whichis optionally substituted with 1 or 2 substituents independentlyselected from halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂ andC(O)NHC₁-C₆alkyl;

A is 5 or 6 member heteroaryl, which heteroaryl comprises one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, which heteroaryl is optionally substituted with 0, 1, 2,3 or 4 groups independently selected from halogen, cyano, C₁-C₆alkyl,C₂-C₆alkenyl. C₂-C₆alkynyl, C₃-C₆cycloalkyl, haloC₁-C₆alkyl,C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)N(R^(A))₂, S(O)₂C₁-C₆alkyl, phenyl or5 or 6 member heteroaryl having one ring heteroatom selected from N, Oor S and 0, 1 or 2 additional ring nitrogen atoms, wherein the optionalheteroaryl or phenyl substituent is further substituted with 0, 1 or 2C₁-C₆alkyl; or

A is phenyl substituted with 1, 2 or 3 substituents independentlyselected from halogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,haloC₁-C₆alkyl, cyanoC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy,cyanoC₁-C₆ alkoxy, S(O)_(q)C₁-C₆alkyl, S(O)₂NH₂. S(O)₂NHC₁-C₆alkyl,S(O)₂N(C₁-C₆alkyl)₂. C(O)NH₂, C(O)NHC₁-C₆alkyl, C(O)N(C₁-C₆alkyl)₂,hydroxy, cyano, or 5 or 6 member heteroaryl having one ring heteroatomselected from N, O or S and 0, 1 or 2 additional ring nitrogen atomswhich heteroaryl is further substituted with 0, 1 or 2 C₁-C₆alkyl; or

A is C(O)OR⁹ or C(O)NR⁹R¹⁰; or

A is optionally substituted 9 or 10 member aromatic or partiallyunsaturated bicycle having 0, 1 or 2 ring nitrogen atoms and 0 or 1additional ring heteroatoms selected from N, O or S, which bicycle issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl,C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂,C(O)OH or C(O)NHC₁-C₆alkyl:

R^(A) is independently selected at each occurrence from hydrogen orC₁-C₄alkyl; or

N(R^(A))₂, taken in combination, forms a 4 to 7 member azacycle which isoptionally substituted with 0, 1, or 2 C₁-C₄alkyl;

R⁷ is hydrogen, C₁-C₄alkyl or amino;

R⁸ is hydrogen or C₁-C₄alkyl; or

CR⁷R⁸, taken in combination form a 3 to 6 member cycloalkandiyl group;

R⁹ is hydrogen, C₁-C₆alkyl, C₃-C₆cycloalkyl, hydroxyC₁-C₆alkyl,C₁-C₄alkoxyC₁-C₆alkyl, haloC₁-C₆alkyl, cyano C₁-C₆alkyl or—(CH₂)_(r)R^(9A) wherein r is 0 or 1 and R^(9A) is phenyl, 4 to 7 memberheterocycle having one ring heteroatoms selected from N, O or S, whichring sulfur may be optionally oxidized, and 0 or 1 additional ring Natoms or 5 or 6 member heteroaryl having one ring heteroatom selectedfrom N, O or S and 0, 1, or 2 additional ring N atoms, which phenyl,heterocycle or heteroaryl is optionally substituted with 0, 1 or 2halogen, C₁-C₄alkyl or C(O)C₁-C₄alkyl;

R¹⁰ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl. C₂-C₆alkynyl, haloC₁-C₆alkyl, C₃-C₇cycloalkyl or saturated, partially unsaturated oraromatic 5 or 6 member heterocycle having 1 or 2 ring heteroatomsindependently selected from N, O and S, which sulfur is optionallyoxidized, and which heterocycle is optionally substituted with 1 or 2substituents independently selected from C₁-C₆alkyl and halogen, whichheterocycle has 1 or 2 ring hetero atoms selected from N, O or S, whichsulfur may be optionally oxidized, and wherein each alkyl or cycloalkylis optionally substituted with cyano, halogen, hydroxy, C₁-C₆alkoxy,S(O)_(q)C₁-C₆alkyl, 4 to 6 member heterocycle having 1 or 2 ringheteroatoms selected from N, O or S or 5 or 6 member heteroaryl having 1ring heteroatom selected from N. O or S and 0, 1 or 2 additional ringnitrogen atoms and where each heterocycle or heteroaryl is optionallysubstituted with 0, 1, or 2 C₁-C₄alkyl; or

NR⁹R¹⁰, taken in combination, form a monocyclic or bicyclic 4 to 10member saturated or partially unsaturated heterocycle having one or tworing nitrogen atoms and 0 or 1 additional ring heteroatom selected fromN, O or S, which ring sulfur may be optionally oxidized, whichheterocycle is optionally substituted with 0, 1 or 2 substitutentsselected from halogen, oxo, hydroxy, cyano, C₁-C₆alkyl, C₁-C₆cycloalkyl,haloC₁-C₆alkyl, hydroxyC₁-C₆alkyl, cyanoC₁-C₆alkyl, C₁-C₆alkoxy,haloC₁-C₆alkoxy, C₁-C₆alkoxyC₁-C₄alkyl, S(O)_(q)C₁-C₆alkyl,C₁-C₆alkylS(O)_(q)C₁-C₆alkyl CO₂H, C(O)C₁-C₆alkyl, C(O)OC₁-C₆alkyl,C(O)C₃-C₆cycloalkyl, N(R¹⁵)C(O)C₁-C₆alkyl or C(O)N(R¹⁵)₂, phenyl, 4 to 6member heterocycle having 1 or 2 ring heteroatoms selected from N, O orS or a 5 or 6 member heteroaryl having 1 ring heteroatom selected fromN, O or S and 0, 1 or 2 additional ring nitrogen atoms and where eachheterocycle or heteroaryl is optionally substituted with 0, 1, or 2C₁-C₁alkyl;

q is 0, 1 or 2;

Z¹ is N or CR¹¹;

Z² is N or CR¹²:

Z³ is N or CR¹³:

Z⁴ is N or CR¹⁴,

Z⁵ and Z⁶ are each independently N or C;

wherein 0, 1 or 2 of Z¹, Z², Z³, Z⁴, Z⁵ and Z⁶ are N;

each of R¹¹, R¹², R¹³ and R¹⁴ is independently selected from the groupconsisting of hydrogen, halogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,C₁-C₆alkoxy, haloC₁-C₆alkyl, haloC₁-C₆alkoxy, C₃-C₇cycloalkyl, cyano,SO₂C₁-C₆alkyl, phenyl, and saturated, partially unsaturated or aromatic5 or 6 member heterocycle having 1 or 2 ring heteroatoms independentlyselected from N, O and S, which heterocycle is optionally substitutedwith 1 or 2 substituents independently selected from C₁-C₆alkyl andhalogen; and

R¹⁵ is selected at each occurrence from hydrogen or C₁-C₄alkyl orN(R¹⁵)₂ taken in combination form a 4 to 7 member azacycle optionallysubstituted with 0, 1 or 2 C₁-C₄alkyl; with the proviso that compoundsof Formula I do not include1-[7-fluoro-6-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-1H-benzimidazol-2-yl]-3-piperidinamine.

In a second embodiment of the invention, compounds and salts accordingto Formula I are provided which are generally represented by thestructure:

Wherein

p is 0 or 1;

when p is 0, then R¹ is hydrogen, C₁-C₆alkyl, halogen or hydroxy; R² isamino or aminoC₁-C₄alkyl; R³ is hydrogen; and R⁴ is hydrogen, C₁-C₆alkylor phenyl; or

when p is 0, then R¹ and R³, taken in combination, form a fusedC₃-C₆cycloalkyl ring or a fused 4 to 6 member heterocycle ring having 1or 2 ring heteroatoms independently selected from N, O or S, whichcycloalkyl or heterocycle is optionally substituted with amino; R² ishydrogen, C₁-C₆alkyl or aminoC₁-C₄alkyl; and R⁴ is hydrogen; or

when p is 1, then R¹ is NHR^(1a); R^(1a) is hydrogen, C₁-C₄alkyl,C₃-C₇cycloalkyl, hydroxyC₁-C₄alkyl, or 4 to 6 member heterocycloalkylhaving one ring heteroatom selected from N, O or S; R² is hydrogen,C₁-C₄alkyl, hydroxyC₁-C₄alkyl or C(O)NH₂; R³ is hydrogen, halogen,C₁-C₄alkyl, C₁-C₄alkoxy or hydroxy; and R⁴ is hydrogen. C₁-C₄alkyl orhalogen; or

when p is 0 or 1, then C(NHR^(1a))R², taken in combination, form aspirocyclic 4 to 6 member heterocycloalkyl; R³ is hydrogen, halogenC₁-C₄alkyl, C₁-C₄alkoxy, or hydroxy; and R⁴ is hydrogen or halogen; or

when p is 1, then R¹ and R³, taken in combination, form a fused 4 to 6member heterocycle or a fused 3 to 7 member carbocycle, whichheterocycle comprises a ring nitrogen atom and optionally 0 or 1additional ring heteroatoms selected from N, O and S, and whichcarbocycle is substituted with amino; and R² is hydrogen; and R⁴ ishydrogen, halogen or hydroxy;

R⁵ represents 1 or 2 substituents independently selected from hydrogen,halogen, hydroxy, amino. C₁-C₆alkyl or C₁-C₆alkoxy;

R⁶ is —(CR⁷R⁸)-A; or

R⁶ is a 4 to 7 member lactam which is optionally substituted with one ortwo substituents independently selected from the group consisting ofhydroxy. C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, haloC₁-C₆alkyl,C₁-C₆alkoxy, haloC₁-C₆alkoxy, hydroxyC₁-C₆alkyl, C₁-C₆alkoxyC₁-C₆alkyl,phenyl or 5 or 6 member heteroaryl having one ring heteroatom selectedfrom N, O or S and 0 or 1 additional ring nitrogen atom, wherein theheteroaryl or phenyl group is optionally substituted with 0, 1 or 2C₁-C₆alkyl or halogen; or

R⁶ is a partially unsaturated 9 or 10 member bicyclic carbocycle, whichis optionally substituted with 1 or 2 substituents independentlyselected from halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,haloC₁-C₆alkyl C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂ andC(O)NHC₁-C₆alkyl;

A is 5 or 6 member heteroaryl, which heteroaryl comprises one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, which heteroaryl is optionally substituted with 0, 1, 2,3 or 4 groups independently selected from halogen, cyano, C₁-C₆alkyl,C₂-C₆alkenyl. C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy,haloC₁-C₆alkoxy, C(O)NH₂, C(O)NHC₁-C₆alkyl, phenyl or 5 or 6 memberheteroaryl having one ring heteroatom selected from N, O or S and 0, 1or 2 additional ring nitrogen atoms, wherein the optional heteroaryl orphenyl substituent is further substituted with 0, 1 or 2 C₁-C₆alkyl; or

A is phenyl substituted with 1, 2 or 3 substituents independentlyselected from halogen, C₁-C₆alkyl, C₂-C₆alkenyl. C₂-C₆alkynyl,haloC₁-C₆alkyl, cyanoC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy,cyanoC₁-C₆ alkoxy, S(O)_(q)C₁-C₆alkyl, S(O)₂NH₂, S(O)₂NHC₁-C₆alkyl,S(O)₂N(C₁-C₆alkyl)₂, C(O)NH₂, C(O)NHC₁-C₆alkyl, C(O)N(C₁-C₆alkyl)₂,hydroxy, cyano, or 5 or 6 member heteroaryl having one ring heteroatomselected from N, O or S and 0, 1 or 2 additional ring nitrogen atomswhich heteroaryl is further substituted with 0, 1 or 2 C₁-C₆alkyl; or

A is C(O)OR⁹ or C(O)NR⁹R¹⁰; or

A is optionally substituted 9 or 10 member aromatic or partiallyunsaturated bicycle having 0, 1 or 2 ring nitrogen atoms and 0 or 1additional ring heteroatoms selected from N, O or S, which bicycle issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl,C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂,C(O)OH or C(O)NHC₁-C₆alkyl;

R⁷ is hydrogen, C₁-C₄alkyl or amino;

R⁸ is hydrogen or C₁-C₄alkyl; or

CR⁷R⁸, taken in combination form a 3 to 6 member cycloalkandiyl group;

R⁹ is hydrogen, C₁-C₆alkyl, hydroxyC₁-C₆alkyl, haloC₁-C₆alkyl or cyanoC₁-C₆alkyl;

R¹⁰ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, haloC₁-C₆alkyl, C₃-C₇cycloalkyl or 4 to 7 member heterocycle, whichheterocycle has 1 or 2 ring hetero atoms selected from N, O or S, whichsulfur may be optionally oxidized, and wherein each alkyl or cycloalkylis optionally substituted with cyano, halogen, hydroxy, C₁-C₆alkoxy,S(O)_(q)C₁-C₆alkyl, 4 to 6 member heterocycle having 1 or 2 ringheteroatoms selected from N, O or S or 5 or 6 member heteroaryl having 1ring heteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms; or

NR⁹R¹⁰, taken in combination, form a monocyclic or bicyclic 4 to 9member heterocycle having one ring nitrogen atom and 0 or 1 additionalring heteroatom selected from N, O or S, which ring sulfur may beoptionally oxidized, which heterocycle is optionally substituted with 0,1 or 2 substitutents selected from halogen, oxo, hydroxy, cyano,C₁-C₆alkyl, halo C₁-C₆alkyl, hydroxyC₁-C₆alkyl, C₁-C₆alkoxy,S(O)_(q)C₁-C₆alkyl, CO₂H, C(O)C₁-C₆alkyl, or C(O)NH₂;

q is 0, 1 or 2;

Z¹ is N or CR¹¹:

Z² is N or CR¹²:

Z³ is N or CR¹³;

Z⁴ is N or CR¹⁴,

Z⁵ and Z⁶ are each independently N or C;

wherein 0, 1 or 2 of Z¹, Z², Z³, Z⁴, Z⁵ and Z⁶ are N;

each of R¹¹, R¹², R¹³ and R¹⁴ is independently selected from the groupconsisting of hydrogen, halogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,C₁-C₆alkoxy, haloC₁-C₆alkyl, haloC₁-C₆alkoxy, C₃-C₇cycloalkyl, cyano,SO₂C₁-C₆alkyl, phenyl, and saturated, partially unsaturated or aromatic5 or 6 member heterocycle having 1 or 2 ring heteroatoms independentlyselected from N, O and S, which heterocycle is optionally substitutedwith 1 or 2 substituents independently selected from C₁-C₆alkyl andhalogen; and with the proviso that compounds of Formula I do not include1-[7-fluoro-6-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-1H-benzimidazol-2-yl]-3-piperidinamine.

The proviso is presented in the first embodiment to specifically excludeand disclaim the identified compound which is indexed as CAS Number1014407-24-9.

In certain aspects of the first or second embodiment, compounds ofFormula I include compounds of Formula Ia:

Where variables p, R¹, R², R³, R⁴, R⁵, R⁶, Z¹, Z², Z³, Z⁴, Z⁵ and Z⁶ areas defined in the first or second embodiment.

In a third embodiment, the invention provides compounds of the first orsecond embodiment in which p is 0; R¹ is hydrogen, C₁-C₆alkyl, halogenor hydroxy; R² is aminoC₁-C₄alkyl; and R³ and R⁴ are hydrogen.

In a fourth embodiment, the invention provides compounds of the first orsecond embodiment in which p is 0; R¹ and R³, taken in combination, forma fused C₃-C₆cycloalkyl ring or a fused 4 to 6 member azacycle ring,which cycloalkyl or azacycle is optionally substituted with amino; andR¹ and R⁴ are hydrogen.

In a fifth embodiment, the invention provides compounds of the fourthembodiment in which R¹ and R³ taken in combination, form a fusedpyrrolidine; and R² and R⁴ are hydrogen.

In a sixth embodiment, the invention provides compounds of the first orsecond embodiment in which p is 1, R¹ is NHR^(1a); R^(1a) is hydrogen.C₁-C₁alkyl, C₃-C₇cycloalkyl or 4 to 6 member heterocycloalkyl having onering heteroatom selected from N, O or S; R² is hydrogen or C₁-C₄alkyl;R³ is hydrogen, halogen. C₁-C₁alkyl, C₁-C₄alkoxy, or hydroxy; and R⁴ ishydrogen, halogen or C₁-C₄alkyl.

In a seventh embodiment, the invention provides compounds of the sixthembodiment in which R¹ is NHR^(1a); R^(1a) is hydrogen, methyl, ethyl,propyl, isopropyl or cyclopropyl; R² is hydrogen or methyl; R³ ishydrogen, halogen, methyl, ethyl, methoxy, ethoxy, or hydroxy; and R⁴ ishydrogen, halogen, methyl or ethyl. In certain aspects of the seventhembodiment, compounds are provided in wich R^(1a) is hydrogen or methyl;R² is hydrogen, R³ is hydrogen, fluorine, methyl or hydroxy; and R⁴ ishydrogen, halogen, methyl or eethyl.

In an eighth embodiment, the invention provides compounds of the sixthor seventh embodiment in which R¹ is NH₂; R² is hydrogen; R³ ishydrogen, fluorine, methyl, or hydroxy; and R⁴ is hydrogen, fluorine ormethyl.

In a ninth embodiment, the invention provides compounds of the first orsecond embodiment in which p is 1; CR¹R², taken in combination, form aspirocyclic 4 to 6 member heterocycloalkyl; R³ is hydrogen, halogen orC₁-C₄alkyl, C₁-C₄alkoxy, hydroxy; and R⁴ is hydrogen or halogen.

In a tenth embodiment, the invention provides compounds of the first orsecond embodiment in which p is 1; R¹ and R³, taken in combination, forma fused 4 or 5 member carbocycle substituted with amino; and R² and R⁴are hydrogen.

In an eleventh embodiment, the invention provides compounds of any oneof the first to tenth embodiment in which R⁵ represents 1 or 2substitutents independently selected from hydrogen, halogen, hydroxy,C₁-C₄alkyl.

In a twelfth embodiment, the invention provides compounds of theeleventh embodiment in which R⁵ represent hydrogen.

In a thirteenth embodiment, the invention provides compounds of any oneof the first to twelfth embodiment in which wherein R⁶ is —(CR⁷R⁸)-A.

In a fourteenth embodiment, the invention provides compounds of thethirteenth embodiment in which R⁷ is hydrogen, methyl or ethyl; R⁸ ishydrogen, or CR⁷R⁸, taken in combination form a cyclopropandiyl group.

In a fifteenth embodiment, the invention provides compounds of thethirteenth or fourteenth embodiment in which R⁷ is hydrogen or methyl;and R⁸ is hydrogen.

In a sixteenth embodiment, the invention provides compounds of any oneof the thirteenth to fifteenth embodiment in which A is 5 or 6 memberheteroaryl, which heteroaryl comprises one ring heteroatom selected fromN, O or S and 0, 1 or 2 additional ring nitrogen atoms, which heteroarylis optionally substituted with 0, 1, or 2 groups independently selectedfrom halogen, cyano, C₁-C₄alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂, C(O)NHC₁-C₄alkyl,phenyl or 5 or 6 member heteroaryl having one ring heteroatom selectedfrom N, O or S and 0, 1 or 2 additional ring nitrogen atoms, wherein theoptional heteroaryl or phenyl substituent is further substituted with 0,1 or 2 C₁-C₆alkyl.

In a seventeenth embodiment, the invention provides compounds of thesixteenth embodiment in which A is pyridin-2-yl, pyridin-3-yl,pyrimidin-2-yl, or pyrazin-2-yl, each of which is substituted with 1 to3 groups independently selected from the group consisting of halogen,cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkoxy,C(O)NH₂, C(O)NHC₁-C₄alkyl, phenyl or 5 member heteroaryl having one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, wherein the optional heteroaryl or phenyl substituent isfurther substituted with 0, 1 or 2 C₁-C₆alkyl.

In an eighteenth embodiment, the invention provides compounds of any oneof the thirteenth to fifteenth embodiment in which A is phenylsubstituted with 1, 2 or 3 substituents independently selected fromhalogen, C₁-C₆alkyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy,hydroxy, cyano, or 5 or 6 member heteroaryl having one ring heteroatomselected from N, O or S and 0, 1 or 2 additional ring nitrogen atomswhich heteroaryl is further substituted with 0, 1 or 2 C₁-C₆alkyl.

In a nineteenth embodiment, the invention provides compounds of theeighteenth embodiment in which A is phenyl substituted with onesubstituent selected from the group consisting of halogen, C₁-C₄alkyl,haloC₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkoxy, hydroxy, cyano, or 5member heteroaryl having one ring heteroatom selected from N, O or S and0, 1 or 2 additional ring nitrogen atoms, and wherein the phenyl groupis further optionally substituted with halogen, C₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkyl or haloC₁-C₄alkoxy.

In a twentieth embodiment, the invention provides compounds of theeighteenth or nineteenth embodiment in which A is phenyl substitutedwith 1 or 2 substituents independently selected from halogen.C₁-C₃alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkoxy, hydroxy orcyano.

In a twenty-first embodiment, the invention provides compounds of anyone of the thirteenth to fifteenth embodiment in which A is C(O)NR⁹R¹⁰;

R⁹ is hydrogen, or C₁-C₄alkyl;

R¹⁰ is C₁-C₄alkyl, haloC₁-C₄alkyl, C₃-C₇cycloalkyl or 4 to 7 memberheterocycle, which heterocycle has 1 or 2 ring hetero atoms selectedfrom N, O or S, which sulfur may be optionally oxidized, and whereineach alkyl or cycloalkyl is optionally substituted with cyano, halogen,hydroxy, C₁-C₆alkoxy, S(O)_(q)C₁-C₆alkyl; or

NR⁹R¹⁰, taken in combination, form a monocyclic or bicyclic 4 to 9member azacycle having one ring nitrogen atom and 0 or 1 additional ringheteroatom selected from N, O or S, which ring sulfur may be optionallyoxidized, which azacycle is optionally substituted with 0, 1 or 2substitutents selected from halogen, oxo, hydroxy, cyano, C₁-C₆alkyl,halo C₁-C₆alkyl, hydroxyC₁-C₆alkyl, C₁-C₆alkoxy. S(O)₂C₁-C₆alkyl, CO₂H,C(O)C₁-C₆alkyl, or C(O)NH₂.

In a twenty second embodiment, the invention provides compounds of thetwenty first embodiment in which R⁹ is hydrogen, methyl or ethyl; and

R¹⁰ is C₁-C₄alkyl or haloC₁-C₄alkyl wherein each alkyl is optionallysubstituted with cyano, halogen, hydroxy, C₁-C₆alkoxy orS(O)_(q)C₁-C₆alkyl.

In a twenty third embodiment, the invention provides compounds of thetwenty first embodiment in which NR⁹R¹⁰, taken in combination, form a 4to 6 member monocyclic azacycle or a 7 to 9 member bicyclic azacycle,each of which having one ring nitrogen atom and 0 or 1 additional ringheteroatom selected from N, O or S, which ring sulfur may be optionallyoxidized, wherein each azacycle is optionally substituted with 0, 1 or 2substitutents selected from halogen, oxo, hydroxy, cyano, C₁-Calkyl,halo C₁-C₆alkyl, hydroxyC₁-C₆alkyl, C₁-C₆alkoxy, S(O)₂C₁-C₆alkyl. CO₂H,C(O)C₁-Calkyl, or C(O)NH₂.

In a twenty fourth embodiment, the invention provides compounds of thetwenty third embodiment in which the 4 to 6 member monocyclic azacyle isselected from the group consisting of:

In a twenty fifth embodiment, the invention provides compounds of thetwenty third embodiment in which the 7 to 9 member bicyclic azacyle isselected from the group consisting of:

In a twenty sixth embodiment, the invention provides compounds of anyone of the first to twelfth embodiment in which R⁶ is a2-oxo-pyrollidin-3-yl or 2-oxo-piperidin-3-yl each of which issubstituted at nitrogen with C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, hydroxyC₁-C₆alkyl,C₁-C₆alkoxyC₁-C₆alkyl, phenyl or 5 or 6 member heteroaryl having onering heteroatom selected from N, O or S and 0 or 1 additional ringnitrogen atom, wherein the heteroaryl or phenyl group is optionallysubstituted with 0, 1 or 2 C₁-C₆alkyl or halogen.

In a twenty seventh embodiment, the invention provides compounds of thetwenty sixth embodiment in which

R⁶ is

Wherein t is 1 or 2; and

R¹⁹ is C₁-C₆alkyl, phenyl substituted with 0, 1 or 2 halogen.

In a twenty eighth embodiment, the invention provides compounds of anyone of the first to twenty seventh embodiment in which Z¹ is CR¹¹;

Z² is CR¹²;

Z³ is CR¹³;

Z⁴ is N or CR¹⁴,

Z⁵ and Z⁶ are each C;

R¹¹ is hydrogen, halogen, cyano or C₁-C₄alkyl;

R¹² and R¹³ are each independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkoxy, C₁-C₆cycloalkyl or 5 member saturated, partiallyunsaturated or aromatic 5 or 6 member heterocycle having 1 or 2 ringheteroatoms independently selected from N, O and S; and

R¹⁴ is hydrogen, halogen, cyano or C₁-C₄alkyl.

In certain aspects of the twenty eighth embodiment, compounds areprovided in which R¹¹ is hydrogen.

In certain other aspects of the twenty eighth embodiment, compounds areprovided in which R¹⁴ is hydrogen, fluorine, chlorine, methyl or cyano.In certain aspects of the twenty eighth embodiment, compounds areprovided in which R¹² and R¹³ are each independently selected from thegroup consisting of hydrogen, fluorine, chlorine, cyano, C₁-C₄alkyl,haloC₁-C₄alkyl, C₁-C₄alkoxy, and haloC₁-C₄alkoxy.

In yet other aspects of the twenty eighth embodiment, compounds areprovided in which R¹¹ is hydrogen; R¹⁴ is hydrogen, fluorine, chlorine,methyl or cyano; and R¹² and R¹³ are each independently selected fromthe group consisting of hydrogen, fluorine, chlorine, cyano, methyl,ethyl, methoxy, ethoxy, fluoromethyl, difluoromethyl, trifluoromethyl,fluoromethoxy, difluoromethoxy, and tifluoromethoxy.

In a twenty ninth embodiment, the invention provides compounds of thefirst or second embodiment which include compounds of Formula II:

Wherein

R¹ is NHR^(1a);

R^(1a) is hydrogen, C₁-C₄alkyl, C₃-C₇cycloalkyl or 4 to 6 memberheterocycloalkyl having one ring heteroatom selected from N, O or S;

R² is hydrogen or C₁-C₄alkyl;

R³ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₄alkoxy, or hydroxy:

R⁴ is hydrogen or halogen;

R⁷ is hydrogen, methyl or ethyl;

A is C(O)NR⁹R¹⁰; or

A is 5 or 6 member heteroaryl, which heteroaryl comprises one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, which heteroaryl is optionally substituted with 0, 1, or2 groups independently selected from halogen, cyano, C₁-C₆alkyl,C₂-C₆alkenyl. C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy,haloC₁-C₆alkoxy, C(O)NH₂, C(O)NHC₁-C₆alkyl, phenyl or 5 or 6 memberheteroaryl having one ring heteroatom selected from N, O or S and 0, 1or 2 additional ring nitrogen atoms, wherein the optional heteroaryl orphenyl substituent is further substituted with 0, 1 or 2 C₁-C₆alkyl; or

A is phenyl substituted with one substituent selected from the groupconsisting of halogen, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkoxy, hydroxy, cyano, or 5 member heteroaryl having one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, and wherein the phenyl group is further optionallysubstituted with halogen, C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkyl orhaloC₁-C₄alkoxy.

R⁹ is hydrogen, or C₁-C₄alkyl;

R¹⁰ is C₁-C₄alkyl, haloC₁-C₄alkyl, C₃-C₇-cycloalkyl or 4 to 7 memberheterocycle, which heterocycle has 1 or 2 ring hetero atoms selectedfrom N, O or S, which sulfur may be optionally oxidized, and whereineach alkyl or cycloalkyl is optionally substituted with cyano, halogen,hydroxy, C₁-C₆alkoxy, S(O)_(q)C₁-C₆alkyl; or

NR⁹R¹⁰, taken in combination, form a monocyclic or bicyclic 4 to 9member azacycle having one ring nitrogen atom and 0 or 1 additional ringheteroatom selected from N, O or S, which ring sulfur may be optionallyoxidized, which azacycle is optionally substituted with 0, 1 or 2substitutents selected from halogen, oxo, hydroxy, cyano, C₁-C₆alkyl,halo C₁-C₆alkyl, hydroxyC₁-C₆alkyl, C₁-C₆alkoxy, S(O)₂C₁-C₆alkyl, CO₂H,C(O)C₁-C₆alkyl, or C(O)NH₂;

Z⁴ is CR¹⁴ or N;

R¹¹ is hydrogen, halogen, cyano or C₁-C₄alkyl:

R¹² and R¹³ are each independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkoxy, C₃-C₆cycloalkyl or 5 member saturated, partiallyunsaturated or aromatic 5 or 6 member heterocycle having 1 or 2 ringheteroatoms independently selected from N, O and S; and

R¹⁴ is hydrogen, halogen, cyano or C₁-C₄alkyl.

In certain aspects of the twenty ninth embodiment, compounds of Formula(II) include compounds of Formula (IIa):

In a thirtieth embodiment, the invention provides compounds of thetwenty ninth embodiment which include compounds of Formula III:

Wherein

X¹ is CR¹⁶ or N;

X² is CR¹⁷ or N;

X³ is CR¹⁸ or N;

Z⁴ is N or CR¹⁴;

R¹ is NHR^(1a);

R^(1a) is hydrogen or C₁-C₄alkyl;

R² is hydrogen or C₁-C₄alkyl:

R³ is hydrogen or halogen;

R⁴ is hydrogen or halogen,

R⁷ is hydrogen, methyl or ethyl;

R¹¹ is hydrogen, halogen, cyano or C₁-C₄alkyl;

R¹² and R¹³ are each independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, orhaloC₁-C₄alkoxy:

R¹⁴ is hydrogen, halogen, cyano or C₁-C₄alkyl;

R¹⁵ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkyl, haloC₁-C₄alkoxy, C(O)NH₂, C(O)NH(C₁-C₄alkyl) or 5 memberheteroaryl having one ring heteroatom selected from N, O or S and 0, 1or 2 additional ring nitrogen atoms;

R¹⁶ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkylor haloC₁-C₄alkoxy;

R¹⁷ is hydrogen or halogen; and

R¹⁸ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkylor haloC₁-C₄alkoxy, wherein at least one of R¹⁵, R¹⁶, R¹⁷ or R¹⁸ is nothydrogen.

In certain aspects of the thirtieth embodiment, compounds of Formula(III) include compounds of Formula (IIIa):

In certain other aspects of the thirtieth embodiment, compounds ofFormula (III) include compounds of Formula (IIIb):

In certain other aspects of the thirtieth embodiment, compounds ofFormula (IIIb) include compounds of Formula (IIIc):

In a thirty first embodiment, the invention provides compounds of thetwenty ninth or thirtieth embodiment in which R² is hydrogen, R⁷ ishydrogen or methyl; and Z⁴ is CR¹⁴.

In a thirty second embodiment, the invention provides compounds of thetwenty ninth embodiment which include compounds of Formula (IV):

Wherein:

R^(1a) is hydrogen or C₁-C₄alkyl;

R³ is hydrogen or halogen;

R⁴ is hydrogen or halogen;

R⁷ is hydrogen, methyl or ethyl;

R¹¹ is hydrogen, halogen, cyano or C₁-C₄alkyl;

R¹² and R¹³ are each independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, orhaloC₁-C₄alkoxy;

R¹⁴ is hydrogen, halogen, cyano or C₁-C₄alkyl; and

R¹⁵ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkyl, haloC₁-C₄alkoxy, C(O)NH₂, or C(O)NH(C₁-C₄alkyl).

In certain aspects of the thirty second embodiment, compounds of Formula(IV) include compounds of Formula (IVa):

In a thirty third embodiment, the invention provides compounds of thetwenty ninth embodiment which include compounds of Formula (V):

Wherein:

R^(1a) is hydrogen or C₁-C₄alkyl;

R³ is hydrogen or halogen;

R⁴ is hydrogen or halogen;

R⁷ is hydrogen, methyl or ethyl;

R¹¹ is hydrogen, halogen, cyano or C₁-C₄alkyl:

R¹² and R¹³ are each independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, orhaloC₁-C₄alkoxy:

R¹⁴ is hydrogen, halogen, cyano or C₁-C₄alkyl; and

R¹⁵ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkyl, haloC₁-C₄alkoxy, C(O)NH₂, or C(O)NH(C₁-C₄alkyl).

In certain aspects of the thirty third embodiment, compounds of Formula(V) include compounds of Formula (Va):

In a thirty fourth embodiment, the invention provides compounds of thetwenty ninth embodiment which include compounds of Formula (VI):

Wherein

R^(1a) is hydrogen or C₁-C₄alkyl;

R³ is hydrogen or halogen;

R⁴ is hydrogen or halogen;

R⁷ is hydrogen, methyl or ethyl;

R¹¹ is hydrogen, halogen, cyano or C₁-C₄alkyl;

R¹² and R¹³ are each independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₁alkyl, C₁-C₄alkoxy, orhaloC₁-C₄alkoxy:

R¹⁴ is hydrogen, halogen, cyano or C₁-C₄alkyl;

R¹⁵ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkyl, haloC₁-C₄alkoxy, C(O)NH₂, C(O)NH(C₁-C₄alkyl) or 5 memberheteroaryl having one ring heteroatom selected from N, O or S and 0, 1or 2 additional ring nitrogen atoms;

R¹⁶ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkylor haloC₁-C₄alkoxy;

R¹⁷ is hydrogen or halogen; and

R¹⁸ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkylor haloC₁-C₄alkoxy,

wherein at least one of R¹⁵, R¹⁶, R¹⁷ or R¹⁸ is not hydrogen.

In certain aspects of the thirty fourth embodiment, compounds of Formula(VI) include compounds of Formula (VIa):

In a thirty fifth embodiment, the invention provides compounds of thetwenty ninth embodiment which include compounds of Formula (VII):

Wherein

R^(1a) is hydrogen or C₁-C₄alkyl;

R³ is hydrogen or halogen;

R⁴ is hydrogen or halogen;

R⁷ is hydrogen, methyl or ethyl;

R⁹ is hydrogen, methyl or ethyl;

R¹⁰ is C₁-C₄alkyl or haloC₁-C₄alkyl wherein each alkyl is optionallysubstituted with cyano, halogen, hydroxy, C₁-C₆alkoxy orS(O)_(q)C₁-C₆alkyl; or

NR⁹R¹⁰, taken in combination, form a 4 to 6 member monocyclic azacycleor a 7 to 9 member bicyclic azacycle, each of which having one ringnitrogen atom and 0 or 1 additional ring heteroatom selected from N, Oor S, which ring sulfur may be optionally oxidized, wherein eachazacycle is optionally substituted with 0, 1 or 2 substitutents selectedfrom halogen, oxo, hydroxy, cyano, C₁-C₆alkyl, halo C₁-C₆alkyl,hydroxyC₁-C₆alkyl, C₁-C₆alkoxy, S(O)₂C₁-C₆alkyl, CO₂H, C(O)C₁-C₆alkyl,or C(O)NH₂;

R¹¹ is hydrogen, halogen, cyano or C₁-C₄alkyl;

R¹² and R¹³ are each independently selected from the group consisting ofhydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, orhaloC₁-C₄alkoxy; and

R¹⁴ is hydrogen, halogen, cyano or C₁-C₄alkyl.

In certain aspects of the thirty fifth embodiment, compounds of Formula(VII) include compounds of Formula (VIIa):

In a thirty sixth embodiment, the invention provides compounds of anyone of the twenty ninth to thirty fifth embodiment in which R¹¹ ishydrogen.

In a thirty seventh embodiment, the invention provides compounds of anyone of the thirty first to thirty fifth embodiment in which R^(1a) ishydrogen or methyl; R³ is hydrogen or fluorine; and R⁴ is hydrogen orfluorine.

In a thirty eighth embodiment, the invention provides compounds of thefirst or second embodiment in which the compound is recited in the belowTable A.

Table A

-   (S)-6-((2-(3-aminopiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile:-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-4-carbonitrile;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3S,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-benzol    imidazol-1-yl)methyl)nicotinonitrile;-   (S)-6-((2-(5-amino-3,3-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;    2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile:-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile:-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-5-(trifluoromethyl)-1H-benzol[d]imidazol-1-yl)methyl)nicotinonitrile:-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-6-(trifluoromethyl)-1H-benzol[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3aS,7aR)-hexahydro-1H-pyrrolo[2,3-c]pyridin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3aS,7aS)-hexahydro-1H-pyrrolo[2,3-c]pyridin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3aS,7aS)-hexahydro-1H-pyrrolo[2,3-c]pyridin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile:-   6-((2-((3aS,7aR)-hexahydro-1H-pyrrolo[2,3-c]pyridin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-(1,6-diazaspiro[3.5]nonan-6-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-6-((2-(1,6-diazaspiro[3.5]nonan-6-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (3R,4R)-1-(1-((5-chloropyridin-2-yl)methyl)-6-(methylsulfonyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((5-chloropyridin-2-yl)methyl)-5-(methylsulfonyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyridin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   (3R,4R)-1-(5,7-difluoro-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(4,6-difluoro-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(5,7-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(4,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-4-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-4-carbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (3R,4S)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4S)-1-(1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   tert-butyl    ((3R,4R)-1-(1-((5-cyanopyridin-2-yl)methyl)-5,6-dimethyl-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate;-   (S)-6-((2-(3-aminopiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (S)-6-((2-(3-aminopiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (S)-2-(3-aminopiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (S)-2-(3-aminopiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-14-(5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-4,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-4,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-(2-(3-amino-4,4-difluoropiperidin-1-yl)-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-(2-(3-amino-4,4-difluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((1R,5S)-1-(aminomethyl)-3-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((1S,5R)-1-(aminomethyl)-3-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3aR,4R,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3aS,4S,6aR)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3aR,4S,6aS)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3aS,4R,6aR)-4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (R)-6-((2-(3-(aminomethyl)pyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (S)-6-((2-(3-(aminomethyl)pyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5,6-dichloro-1H-benzol[dl]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (R)-1-((5-chloropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-amine    hydrochloride;-   (3R,4S)-1-(1-((5-chloropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride,    (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-4-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-3H-imidazo[4,5-b]pyridin-3-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-imidazol[4,5-b]pyridin-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-imidazo[4,5-b]pyridin-1-yl)methyl)-N-(tert-butyl)nicotinamide;-   6-((2-((3R,4R)-3-amino-4-hydroxypiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3S,4S)-3-amino-4-hydroxy    piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-(2,6-diazaspiro[3.4]octan-6-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((4aR,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((4aS,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((4aR,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((4aS,7aS)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-3-amino-1-(1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidine-3-carboxamide;-   (R)-3-amino-1-(1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidine-3-carboxamide;-   (S)-6-((2-(3-amino-3-(hydroxy    methyl)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-(3-amino-3-(hydroxymethyl)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoro-1-piperidinyl)-6-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoro-1-piperidinyl)-5-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile.-   6-((2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-6-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-5-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-methyl-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-methyl-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-chloro-5-methyl-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile.-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-chloro-6-methyl-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-fluoro-5-methyl-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-fluoro-6-methyl-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3S)-3-(methylamino)-1-piperidinyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R)-3-(methylamino)-1-piperidinyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-(difluoromethoxy)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-(difluoromethoxy)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methyl-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   5-((2-((3R,4S)-3-amino-4-fluoro-1-piperidinyl)-6-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-2-pyrazinecarboxamide;-   5-((2-((3R,4S)-3-amino-4-fluoro-1-piperidinyl)-5-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-2-pyrazinecarboxamide;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-chloro-5-(trifluoromethoxy)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-chloro-6-(trifluoromethoxy)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-chloro-5-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-chloro-6-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((5R)-1,7-diazaspiro[4.5]decan-7-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile.    6-((2-((5S)-1,7-diazaspiro[4.5]decan-7-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((6R)-1,8-diazaspiro[5.5]undecan-8-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((6S)-1,8-diazaspiro[5.5]undecan-8-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((4aR,8aR)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((4aS,8aS)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   5-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)-2-pyrazinecarboxamide;-   5-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-2-pyrazinecarboxamide;-   6-((2-((5R)-1,7-diazaspiro[4.5]decan-7-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((5S)-1,7-diazaspiro[4,5]decan-7-yl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile.-   6-((2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-5-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-6-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3S)-3-(methylamino)-1-piperidinyl)-6-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3S)-3-(methylamino)-1-piperidinyl)-5-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3S)-3-amino-3-methyl-1-piperidinyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    2,2,2-trifluoroacetate;-   (S)-6-((2-(3-aminopiperidin-1-yl)-5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    2,2,2-trifluoroacetate;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4-chloro-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    2,2,2-trifluoroacetate;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazole-7-carbonitrile;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   6-((2-((3R,4R)-3-amino-4-hydroxypiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-hydroxypiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-4-((2-(3-amino-4,4-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-hydroxypiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    compound with    4-((2-((3S,4S)-3-amino-4-hydroxypiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    (1:1) dihydrochloride;-   4-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,7-difluoro-1H-benzimidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4,6-difluoro-1H-benzimidazol-1-yl)methyl)benzonitrile;-   2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-1-(4-cyanobenzyl)-1H-benzimidazole-6-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-1-(4-cyanobenzyl)-1H-benzimidazole-5-carbonitrile;-   2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-1-(4-cyanobenzyl)-1H-benzimidazole-6-carbonitrile;-   2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-1-(4-cyanobenzyl)-1H-benzimidazole-5-carbonitrile;-   (R)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-methylpiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-(3-(aminomethyl)-3-methylpyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3S,4R)-3-amino-4-phenylpyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    &    4-((2-((3R,4S)-3-amino-4-phenylpyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (S)-4-((2-(3-aminopyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (S)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-(6-amino-2-azaspiro[4.4]nonan-2-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-(4-aminohexahydrocyclopenta[c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3S,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3S,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-4-((2-(3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate;-   (S)-4-((2-(3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate.-   (R)-4-((2-(3-(aminomethyl)-3-hydroxypyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate;-   (S)-4-((2-(3-(aminomethyl)-3-hydroxypyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate;-   (S)-4-((2-(3-(aminomethyl)pyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;

Molecular Weight; 331.41;

-   (R)-4-((2-(3-(aminomethyl)pyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;

Molecular Weight; 331.41;

-   4-((2-((3S,4S)-3-amino-4-methylpiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate;-   4-((2-((3S,4R)-3-amino-4-methylpiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate;-   4-((2-((3R,4S)-3-amino-4-methylpiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate;-   4-((2-((1S,5R)-1-(aminomethyl)-3-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((1R,5S)-1-(aminomethyl)-3-azabicyclo[3.1.0]hexan-3-yl)-1H-benzo[d]imidazol-1-yl)methyl)    benzonitrile;-   (R)-4-((2-(3-aminopiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-4-((2-(3-aminopiperidin-1-yl)-5-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-4-fluoro-1-(1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   (3R,4R)-1-(1-((5-bromopyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-4-fluoro-1-(1-((5-(trifluoromethyl)pyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-4-fluoro-1-(1-(1((5-methoxypyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-14-(5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-cyanopyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-bromopyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-bromopyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   5-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)pyrazine-2-carbonitrile;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile;-   (3R,4R)-3-amino-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-4-ol;-   (3R,4R)-3-amino-1-(1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-4-ol;-   6-((2-((3R,4R)-3-amino-4-hydroxypiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-hydroxypiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-1-(1-((5-chloropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (S)-5-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)picolinonitrile;-   (3R,4R)-1-(1-((5-chloropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyridin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyridin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile    hydrochloride;-   (3R,4R)-1-(1-((R)-1-(5-chloropyridin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(1-((S)-1-(5-chloropyridin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(1-((R)-1-(5-chloropyridin-2-yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(1-((S)-1-(5-chloropyridin-2-yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(5-chloro-1-((R)-1-(5-chloropyridin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(5-chloro-1-((S)-1-(5-chloropyridin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(6-chloro-1-((R)-1-(5-chloropyridin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(6-chloro-1-((S)-1-(5-chloropyridin-2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((R)-1-(5-cyanopyridin-2-yl)ethyl)-1H-benzo[d]imidazole-6-carbonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((R)-1-(5-cyanopyridin-2-yl)ethyl)-1H-benzo[d]imidazole-5-carbonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((S)-1-(5-cyanopyridin-2-yl)ethyl)-1H-benzo[d]imidazole-6-carbonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((S)-1-(5-cyanopyridin-2-yl)ethyl)-1H-benzo[d]imidazole-5-carbonitrile    hydrochloride;-   (3R,4R)-1-(1-((5-chloropyridin-2-yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(5,6-difluoro-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine    hydrochloride;-   (R)-1-(1-((5-chloropyridin-2-yl)methyl)-5,7-difluoro-1H-benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-amine    hydrochloride;-   (R)-1-(1-((5-chloropyridin-2-yl)methyl)-4,6-difluoro-1H-benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-amine    hydrochloride;-   (R)-1-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)-2,3-dihydro-1H-indene-5-carbonitrile    hydrochloride;-   (S)-1-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)-2,3-dihydro-1H-indene-5-carbonitrile    hydrochloride;-   (R)-5-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)pyrazine-2-carbonitrile;-   (R)-5-((2-(3-amino-4,4-difluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)methyl)pyrazine-2-carbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-isopropylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(azetidin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2-cyanopropyl)-N-ethylacetamide;-   3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-methylpyrrolidin-2-one;-   3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-phenylpiperidin-2-one;-   3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-chlorophenyl)pyrrolidin-2-one;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-methoxypyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-methoxypyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile    hydrochloride;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-benzo[d]imidazolc-5-carbonitrile    hydrochloride;-   (S)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-methylpyrrolidin-2-one;-   (R)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-methylpyrrolidin-2-one;-   (S)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-chiorophenyl)pyrrolidin-2-one;-   (R)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-chiorophenyl)pyrrolidin-2-one;-   2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-14-(5-cyano-2-pyrazinyl)methyl)-1H-benzimidazole-6-carbonitrile;-   2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-1-((5-cyano-2-pyrazinyl)methyl)-1H-benzimidazole-5-carbonitrile;-   5-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4,6-difluoro-1H-benzimidazol-1-yl)methyl)-2-pyrazinecarbonitrile;-   5-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,7-difluoro-1H-benzimidazol-1-yl)methyl)-2-pyrazinecarbonitrile;-   (3S)-1-(1-((5-fluoro-2-pyridinyl)methyl)-1H-benzimidazol-2-yl)-N-methyl-3-piperidinamine;-   (3S)-1-(l-((5-chloro-2-pyridinyl)methyl)-1H-benzimidazol-2-yl)-N-methyl-3-piperidinamine;-   6-((1R)-1-(2-((3S)-3-(methylamino)-1-piperidinyl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1S)-1-(2-((3S)-3-(methylamino)-1-piperidinyl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   (3R,4R)-1-(1-((5-chloro-2-pyrimidinyl)methyl)-5,7-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((5-chloro-2-pyrimidinyl)methyl)-4,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-((1-methyl-1H-indazol-4-yl)methyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(5-quinolinylmethyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-((1R)-1-(8-quinolinyl)ethyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-((1S)-1-(8-quinolinyl)ethyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((3-(3-chlorophenyl)-1,2-oxazol-5-yl)methyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-((1-methyl-1H-indazol-7-yl)methyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(2,6-dichlorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   1-(1-azetidinyl)-2-(2-((3S)-3-(methylamino)-1-piperidinyl)-1H-benzimidazol-1-yl)ethanone;-   6-((1R)-1-(4,6-difluoro-2-((4aR,8aR)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1R)-1-(4,6-difluoro-2-((4aS,8aS)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1S)-1-(4,6-difluoro-2-((4aS,8aS)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1S)-1-(4,6-difluoro-2-((4aR,8aR)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1R)-1-(5,7-difluoro-2-((4aR,8aR)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1R)-1-(5,7-difluoro-2-((4aS,8aS)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1S)-1-(5,7-difluoro-2-((4aS,8aS)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   6-((1S)-1-(5,7-difluoro-2-((4aR,8aR)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1-yl)ethyl)-3-pyridinecarbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-1-(4-morpholinyl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-1-(1-pyrrolidinyl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-N,N-dimethylacetamide;-   (2R)-2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-N,N-dimethylpropanamide;-   (2S)-2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-N,N-dimethylpropanamide;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-1-(1-piperidinyl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-N-ethylacetamide;-   1-((5-chloro-2-pyrimidinyl)methyl)-2-((3R,4R)-4-fluoro-3-(methylamino)-1-piperidinyl)-1H-benzimidazole-6-carbonitrile;-   1-((5-chloro-2-pyrimidinyl)methyl)-2-((3R,4R)-4-fluoro-3-(methylamino)-1-piperidinyl)-1H-benzimidazole-5-carbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-chloro-1H-benzimidazol-1-yl)-1-(1-azetidinyl)ethanone;-   24(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-chloro-1H-benzimidazol-1-yl)-1-(1-azetidinyl)ethanone;-   2-((3R,4S)-3-amino-4-fluoro-1-piperidinyl)-1-(2-(1-azetidinyl)-2-oxoethyl)-1H-benzimidazole-6-carbonitrile;-   2-((3R,4S)-3-amino-4-fluoro-1-piperidinyl)-1-(2-(1-azetidinyl)-2-oxoethyl)-1H-benzimidazole-5-carbonitrile;-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (R)-6-((2-(3-aminopiperidin-1-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-5-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)picolinonitrile    2,2,2-trifluoroacetate;-   (R)-1-(1-(isoquinolin-7-ylmethyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-((1-methyl-1H-indazol-7-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   6-((R)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile    hydrochloride;-   6-((S)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile    hydrochloride;-   6-((R)-1-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile    hydrochloride;-   6-((S)-1-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile    hydrochloride;-   6-((R)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)propyl)nicotinonitrile    hydrochloride;-   6-((S)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)propyl)nicotinonitrile    hydrochloride;-   (3R,4R)-1-(5,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   3-(1-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile;-   (3R,4R)-1-(5,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4S)-1-(5,6-difluoro-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4S)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4S)-4-fluoro-1-(I-((5-fluoropyrimidin-2-yl)methyl)-5-(trifluoromethyl)-1H-benzol[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(5,6-difluoro-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-amine;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-1-(azetidin-1-yl)ethan-1-one;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-1-(azetidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2,2-dimethylpyrrolidin-1-yl)ethan-1-one;-   6-((2-((3R,4S)-3-amino-4-hydroxypiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-hydroxypiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   4-((R)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile    hydrochloride;-   4-((S)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile    hydrochloride;-   (S)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-3-fluorobenzonitrile    hydrochloride;-   (S)-1-(1-(4-chlorobenzyl    1)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine hydrochloride;-   4-((R)-1-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile    hydrochloride;-   4-((S)-1-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile    hydrochloride;-   4-((R)-1-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile    hydrochloride;-   4-((S)-1-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile    hydrochloride;-   (S)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-3-chlorobenzonitrile    hydrochloride;-   (3R,4R)-1-(1-((1R)-1-(2,4-dichlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1S)-1-(2,4-dichlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1R)-1-(2-chlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1S)-1-(2-chlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(l-((1R)-1-(3-chlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1S)-1-(3-chlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1R)-1-(2,5-dichlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1S)-1-(2,5-dichlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1R)-1-(2,4-difluorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1S)-1-(2,4-difluorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1R)-1-(3,4-dichlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1S)-1-(3,4-dichlorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1R)-1-(2,5-difluorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-((1S)-1-(2,5-difluorophenyl)ethyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-((1R)-1-(4-(trifluoromethyl)phenyl)ethyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-((1R)-1-(4-(trifluoromethoxy)phenyl)ethyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(5-chloro-2-(trifluoromethoxy)benzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(4-(1H-1,2,4-triazol-1-yl)benzyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   2-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)-5-chlorobenzonitrile;-   (3R,4R)-1-(1-(2,4-dichlorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   4-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)-3-(difluoromethoxy)benzonitrile;-   (3R,4R)-1-(1-(2,5-dichlorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(4-(1,1-difluoroethyl)benzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   4-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)-2-methylbenzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)-2-chlorobenzonitrile;-   2-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)-4-chlorobenzonitrile;-   (3R,4R)-1-(I-(2-(difluoromethoxy)benzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(3-chloro-4-fluorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(4-chloro-2-methoxybenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(2,4-difluorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(2-(trifluoromethyl)benzyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   2-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)benzonitrile;-   (3R,4R)-1-(1-(2-chlorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(2-chloro-4-fluorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(4-fluoro-2-(trifluoromethyl)benzyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(3,4-difluorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(4-chloro-2-fluorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(3,4-dichlorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(4-chloro-3-fluorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(4-(trifluoromethyl)benzyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(4-(trifluoromethoxy)benzyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(1-(4-(difluoromethyl)benzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(3-(trifluoromethoxy)benzyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (3R,4R)-1-(5,6-difluoro-1-(3-(trifluoromethyl)benzyl)-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   3-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)methyl)benzonitrile;-   (3R,4R)-1-(1-(3-chlorobenzyl)-5,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   (S)-1-(1-(4-fluorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (S)-1-(1-(4-(1,2,4-oxadiazol-3-yl)benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-(methylsulfonyl)benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-(1H-1,2,4-triazol-1-yl)benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-2-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-1-(1-(2,6-dichlorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(2-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-(trifluoromethoxy)benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(3-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-(1,1-difluoroethyl)benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-2-(4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)phenyl)-2-methylpropanenitrile;-   (R)-1-(1-(4-(difluoromethyl)benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-N-methylbenzamide;-   (R)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-3-fluorobenzonitrile;-   (R)-2-(4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)phenoxy)acetonitrile;-   (R)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-N,N-dimethylbenzenesulfonamide;-   (R)-1-(1-(4-methylbenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-fluorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-((1-methyl-1H-indazol-7-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(2,4-difluorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(3,4-difluorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(4-chloro-3-fluorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-((3-(3-chlorophenyl)isoxazol-5-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-1-(1-(3-chloro-4-methoxy    benzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-4-((2-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-3-chlorobenzonitrile;-   (R)-1-(1-(2,4-dichlorobenzyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (R)-4-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-3-methoxybenzonitrile;-   (R)-2-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)-5-chlorobenzonitrile;-   4-((R)-1-(2-((R)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile;-   4-(1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile;-   (R)-3-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    hydrochloride;-   (S)-4-((2-(3-aminopiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    hydrochloride;-   4-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (S)-4-((2-(3-aminopiperidin-1-yl)-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzonitrile    hydrochloride;-   (R)-4-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-4-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-4-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)    benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-4-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-imidazo[4,5-c]pyridin-1-yl)methyl)    benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-3H-imidazo[4,5-d]pyridine-3-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-ethoxy-1H-benzimidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-imidazo[4,5-b]pyridin-1-yl)methyl)benzonitrile;-   4-((2-((3R)-3-amino-44-difluoro-1-piperidinyl)-6-fluoro-1H-benzimidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-imidazo[4,5-b]pyridin-1-yl)methyl)    benzonitrile;-   (S)-4-((2-(3-aminopiperidin-1-yl)-4-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    2,2,2-trifluoroacetate;-   (S)-4-((2-(3-aminopiperidin-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzonitrile    hydrochloride;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    hydrochloride;-   (S)-4-((2-(3-aminopiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (S)-4-((2-(3-aminopiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)-2,3-dihydro-1H-indene-5-carbonitrile;-   (S)-1-(2-((S)-3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)-2,3-dihydro-1H-indene-5-carbonitrile;-   (3R,4R)-4-fluoro-1-(1-((5-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)azetidine-3-carbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3-(tert-butoxy)azetidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3-isopropylazetidin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(7-oxa-2-azaspiro[3.5]nonan-2-yl)ethanone;-   (R)-6-((2-(4,4-difluoro-3-(methylamino)piperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-4,4-difluoro-3-(2-hydroxyethyl)amino)piperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (S)-6-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinic    acid;-   (S)-6-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinamide;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinamide.    2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetic    acid;-   6-((R)-1-(4,6-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile;-   6-((S)-1-(4,6-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile;-   6-((R)-1-(5,7-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile;    and-   6-((S)-1-(5,7-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile.

In another aspect of the thirty eighth embodiment, the inventionprovides compounds of the first embodiment in which the compound isrecited in the below Table A-1;

Table A-1

-   2-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)pyrimidine-5-carbonitrile;-   2-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)pyrimidine-5-carbonitrile;-   (3R,4R)-4-fluoro-1-(6-fluoro-1-((5-methoxypyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (3R,4R)-4-fluoro-1-(5-fluoro-1-((5-methoxypyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4-cyano-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-methoxy-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-methoxy-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   6-((2-((3R,4R)-3-amino-4-methoxy    piperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-4-methoxy-1H-benzol    imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)nicotinonitrile;-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-methoxy    piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-bromo-1H-benzo[d]imidazol-yl)-1-(azetidin-1-yl)ethan-1-one;-   (3R,4R)-1-(I-(5-chloropyrimidin-2-yl)methyl)-i-fluoro-1H-benzo[d]imidazol-2-yl)-4-methoxypiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-imidazo[4,5-b]pyridin-1-yl)methyl)nicotinonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-1-morpholinoethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   6-((2-((3R,4S)-3-amino-4-methoxypiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-1-morpholinoethan-1-one;-   (R)-2-(2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (3R,4S)-1-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-methoxypiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(6-fluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-bromo-1H-benzo[d]imidazol-1-yl)-1-(azetidin-1-yl)ethan-1-one;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(6-fluoro-2-(1,7-diazaspiro[4.5]decan-7-yl)-1H-benzo[d]imidazol-1-yl)-N-methyl-N-((2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-1-morpholinoethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)-1-morpholinoethan-1-one;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-7-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (3R,4S)-1-(1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)-4-methoxypiperidin-3-amine;-   2-(2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-1-morpholinoethan-1-one;-   2-(5-fluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-(3-amino-4-methylpyrrolidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-hydroxypiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (R)-2-(2-(3-amino-4,4-difluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-methoxypiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R)-3-amino-4-hydroxypiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)-N-methy    1-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-methoxypiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-(3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-(3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(6-fluoro-2-((4aR,8aR)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (S)-2-(2-(3-aminopyrrolidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (R)-2-(2-(3-aminopyrrolidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (S)-2-(2-(3-(aminomethyl)pyrrolidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,    2,2-trifluoroethyl)acetamide;-   2-(6-fluoro-2-((4aR,8aR)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(5-fluoro-2-((4aS,8aS)-hexahydro-2H-pyrido[4,3-b][1,4]oxazin-6(5H)-yl)-1H-benzo[d]imidazol-1-yl)-N-methy    1-N-(2,2,2-trifluoroethyl)acetamide;-   (3R,4R)-3-amino-1-(1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-4-ol;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)-1-morpholinoethanone;-   (3R,4R)-3-amino-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-4-ol;-   -(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)-1-morpholinoethanone;-   (3R,4R)-1-(1-((R)-1-(5-chloropyrimidin-2-yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H-imidazo[4,5-b]pyridin-1-yl)methyl)nicotinonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(thiazol-2-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-(azetidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3-(trifluoromethyl)piperidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-methylmorpholino)ethan-1-one;-   (3R,4R)-1-(1-((R)-1-(5-chloropyrimidin-2-yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-7-methoxy-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(azocan-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(pyrazin-2-yl)piperazin-1-yl)ethan-1-one;-   methyl    1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)piperidine-4-carboxylate;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-ethylmorpholino)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)-1-(azetidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1,1-dioxido-2,3-dihydrothiophen-3-yl)-N-phenylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-methylpiperidin-1-yl)ethan-1-one;-   (3R,4R)-4-fluoro-1-(6-fluoro-1-((4-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-ethylmorpholino)ethan-1-one;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)nicotinonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)-1-(azetidin-1-yl)ethan-1-one;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)piperidine-2-arboxamide;-   24(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-(thiophen-2-ylmethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(octahydroisoquinolin-2(11H)-yl)ethan-1-one;-   (3R,4R)-4-fluoro-1-(5-fluoro-1-((4-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-cyclopropyl-N-(1,1-dioxidotetrahydrothiophen-3-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-ethylacetamide;-   4-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)piperazin-2-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(pyrrolidine-1-carbonyl)piperidin-1-yl)ethan-1-one;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)piperidine-3-carboxamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(cyclopropanecarbonyl)piperazin-1-yl)ethan-1-one;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)piperidine-4-carboxamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2-cyanopropan-2-yl)-N-methylacetamide;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-N-methylpiperidine-4-carboxamide;-   N-(1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)piperidin-3-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(piperidine-1-carbonyl)piperidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(azepane-1-carbonyl)piperidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-(2-methoxyethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(3-methylpiperidine-1-carbonyl)piperidin-1-yl)ethan-1-one;-   1-(4-acetylpiperazin-1-yl)-2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-N-((tetrahydrofuran-2-yl)methyl)acetamide;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-N-isopropyl-N-methylpiperidine-4-carboxamide;-   2-(2-((3R,4R)-3-amino-4-methoxypiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-7-methoxy-1H-benzo[d]imidazol-1-yl)-N-methy    1-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-4-methoxy-1H-benzo[d]imidazol-1-yl)-1-morpholinoethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-7-methoxy-1H-benzo[d]imidazol-1-yl)-1-morpholinoethan-1-one;-   (R)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-cyclopropylpyrrolidin-2-one;-   (S)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-2-one;-   (S)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-cyclopropylpyrrolidin-2-one;-   (R)-3-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-2-one;-   (3R,4R)-1-(5,6-difluoro-1-((5-methylthiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(4,6-difluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(5,6-difluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-imidazo[4,5-b]pyridin-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(4,6-difluoro-1-((5-(methylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)methyl)-4,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,    2,2-trifluoroethyl)acetamide;-   (3R,4R)-1-(1-((5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-4-fluoro-1-(6-fluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-1-(5,6-difluoro-1-((5-(methylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   (3R,4R)-1-(5,6-difluoro-1-((5-methylisoxazol-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   (3R,4R)-1-(5,6-difluoro-1-((5-methyloxazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(5,6-difluoro-1-((4-methylthiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-4-fluoro-1-(6-fluoro-1-((3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-chloro-1H-benzo[d]imidazol-1-yl)-N-methy    1-N-(2,2,2-trifluoroethyl)acetamide;-   (3R,4R)-1-(5,6-difluoro-1-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(5,6-difluoro-1-((5-methyl-1,2,4-oxadiazol-3-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-4-fluoro-1-(6-fluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-imidazo[4,5-b]pyridin-2-yl)piperidin-3-amine;-   (3R,4R)-1-(1-((4,5-dimethyloxazol-2-yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   (3R,4R)-1-(1-((5-ethyl-1,2,4-oxadiazol-3-yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((5-cyclopropyl-1,2,4-oxadiazol-3-yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(5,6-difluoro-1-((3-methylisoxazol-5-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (3R,4R)-1-(1-((5-cyclopropyl-1,3,4-oxadiazol-2-yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-4-fluoro-1-(5-fluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-1-(3-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-3H-imidazo[4,5-b]pyridin-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-4-fluoro-1-(5-fluoro-1-((3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-4-fluoro-1-(6-fluoro-1-((4-methyl-2-phenylthiazol-5-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-1-(1-((4,5-dimethyl-4H-1,2,4-triazol-3-yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (R)-4,4-difluoro-1-(6-fluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-1-(1-((2,4-dimethylthiazol-5-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-4-fluoro-1-(6-fluoro-3-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-3H-imidazo[4,5-b]pyridin-2-yl)piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,7-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   (3R,4R)-4-fluoro-1-(5-fluoro-1-((4-methyl-2-phenylthiazol-5-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,7-difluoro-1H-benzo[d]imidazol-1-yl)-N,N-dimethylacetamide;-   (3R,4R)-1-(5,7-difluoro-1-((5-(methylsulfonyl)pyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((2,4-dimethylthiazol-5-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (R)-4,4-difluoro-1-(5-fluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   (3R,4R)-1-(1-((5-(difluoromethyl)-1,3,4-thiadiazol-2-yl)methyl)-5,7-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(5,7-difluoro-1-((5-methyl-1,3,4-thiadiazol-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-methylazetidin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2,2-difluoroethyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-cyclopropyl-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-((R)-1-cyanoethyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-((R)-1-(pyridin-2-yl)ethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-ethyl-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2-fluoroethyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-((1R,5S)-3-azabicyclo[3.1.0]hexan-3-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(1-(pyridin-2-yl)ethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-azabicyclo[3.1.0]hexan-2-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-((S)-1-cyanoethyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(tetrahydrofuran-3-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1-cyanopropan-2-yl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(1-(pyridin-4-yl)ethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(1,1,1-trifluoropropan-2-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(cyanomethyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methy    1-N-propylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-cyclopropyl-N-(2-hydroxyethyl)acetamide;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-3-fluoropyrrolidin-3-carbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(hexahydropyrano[4,3-b][1,4]oxazin-4(7H)-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2-cyanopropyl)-N-methylacetamide;-   -(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(3,3,3-trifluoropropyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-((1R,5S)-6,6-difluoro-3-azabicyclo[3.1.0]hexan-3-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-isopropylazetidin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3-(difluoromethoxy)pyrrolidin-1-yl)ethanone;-   4-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)morpholine-2-carbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3-hydroxypiperidin-1-yl)ethanone;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-4-methylpiperidine-4-carbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3,4-dihydro-1,8-naphthyridin-1    (2H)-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-cyclopropyl-N-(2,2-difluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-((tetrahydrofuran-3-yl)methyl)acetamide;-   -(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2,2-difluoroethyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2-trifluoroethyl)acetamide;-   (R)-1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)pyrrolidine-2-carbonitrile;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-((1r,4R)-4-hydroxycyclohexyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-((S)-1-(pyridin-2-yl)ethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(octahydro-1H-pyrano[4,3-b]pyridin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-hydroxypiperidin-1-yl)ethanone;-   1-(3-(1H-1,2,4-triazol-1-yl)azetidin-1-yl)-2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)ethanone;-   7-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)hexahydroimhidazo[1,5-a]pyrazin-3(2H)-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2-cyanoethyl)-N-((tetrahydrofuran-3-yl)methyl)acetamide;-   4-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-N-methylmorpholine-2-carboxamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3-((methylsulfonyl)methyl)pyrrolidin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(2-(methoxymethyl)morpholino)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(3-hydroxy-3-methylpyrrolidin-1-yl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-(4-(methylsulfonyl)piperazin-1-yl)ethanone;-   N-((1-acetylpyrrolidin-3-yl)methyl)-2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-ethylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-((1,1-dioxidotetrahydrothiophen-3-yl)methyl)-N-methylacetamide;-   24(1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)piperidin-4-yl)-2-methylpropanenitrile;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-N-methylpiperidine-3-carboxamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2-hydroxyethyl)-N-(pyridin-3-ylmethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N-(2-cyanoethyl)-N-(tetrahydro-2H-pyran-4-yl)acetamide;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-N,N-dimethylpiperidine-3-carboxamide;-   1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)-4-(methoxymethyl)piperidine-4-carbonitrile;-   7-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)tetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzol[dl]imidazol-1-yl)-N-(thiazol-2-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-cyclopropyl-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-(2-methoxyethyl)-N-methylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-((S)-tetrahydrofuran-3-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-methyl-N-((R)-tetrahydrofuran-3-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((S)-1-(pyridin-2-yl)ethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-cyclobutylacetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((S)-1-cyanopropan-2-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((R)-1-cyanopropan-2-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-ethyl-N-(2-methoxyethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)-N-(2,2,2-trifluoroethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((R)-1-(pyridin-2-yl)ethyl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((S)-tetrahydrofuran-3-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-N-((R)-tetrahydrofuran-3-yl)acetamide;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-(2-methylazetidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-((S)-3-methylmorpholino)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-((R)-2-methylpyrrolidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-((R)-3-(methoxymethyl)morpholino)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-((R)-3-methylmorpholino)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-((S)-2-methylpyrrolidin-1-yl)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-(3,5-dimethylmorpholino)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-(3-ethylmorpholino)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-((S)-3-cyclopropylmorpholino)ethan-1-one;-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-((R)-3-(hydroxmethyl)morpholino)ethan-1-one;    and-   2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)-1-(3,3-dimethylmorpholino)ethan-1-one.

In a thirty ninth embodiment, the invention provides compounds of thefirst or second embodiment in which the compound is recited in the belowTable B;

Table B

-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzol[d]imidazol-1-yl)methyl)nicotinonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazole-4-carbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   (3R,4R)-1-(4,6-difluoro-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(4,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-fluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-4-carbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-(2-(3-amino-4,4-difluoropiperidin-1-yl    1)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-imidazo[4,5-b]pyridin-1-yl)methyl)nicotinonitrile;-   6-((2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-6-(trifluoromethyl)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5-(difluoromethoxy)-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-6-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-31)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4,6-difluoro-1H-benzimidazol-1-yl)methyl)benzonitrile;-   4-((2-((3S,4S)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (R)-4-((2-(3-aminopiperidin-1-yl)-6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile;-   (2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazolc-6-carbonitrile;-   (3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (3R,4R)-3-amino-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-4-ol;-   (R)-1-(1-((5-chloropyridin-2-yl)methyl)-4,6-difluoro-1H-benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(1-((5-chloro-2-pyrimidinyl)methyl)-4,6-difluoro-1H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-5,6-difluoro-1H-benzimidazol-1-yl)-1-(1-piperidinyl)ethanone;-   2-(2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-6-chloro-1H-benzimidazol-1-yl)-1-(1-azetidinyl)ethanone;-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(5,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4S)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-6-(trifluoromethyl)-1H-benzol    imidazol-2-yl)piperidin-3-amine; and-   4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile    hydrochloride.

In a fortieth embodiment, the invention provides compounds of the firstor second embodiment in which the compound is recited in the below TableC;

Table C

-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-(trifluoromethoxy)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   (3R,4R)-1-(4,6-difluoro-1-((5-fluoropyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   (3R,4R)-1-(4,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   6-((2-((3R)-3-amino-4,4-difluoro-1-piperidinyl)-6-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   (R)-2-(3-amino-4,4-difluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;-   (2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;-   2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (R)-1-(1-((5-chloropyridin-2-yl)methyl)-4,6-difluoro-1H-benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-amine    hydrochloride;-   (3R,4R)-1-(l-((5-chloro-2-pyrimidinyl)methyl)-4,6-difluoro-H-benzimidazol-2-yl)-4-fluoro-3-piperidinamine;    and-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine.

In a forty first embodiment, the invention provides compounds of thefirst or second embodiment in which the compound is recited in the belowTable D;

Table D

-   6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methy)-6-fluoro-H-benzo[d]imidazole-4-carbonitrile;-   (3R,4R)-1-(4,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;-   6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile    hydrochloride;-   (R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;-   6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;-   (2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;-   (3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;    and-   (3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine.

In a further embodiment, each of the compounds disclosed herein areprovided in the form of a pharmaceutically acceptable salt.

In a forty second embodiment, the invention provides6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.In certain aspects of the forty second embodiment, the inventionprovides a pharmaceutically acceptable salt of6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.

In a forty third embodiment, the invention provides2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile.In certain aspects of the forty third embodiment, the invention providesa pharmaceutically acceptable salt of2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile.

In a forty fourth embodiment, the invention provides(3R,4R)-1-(4,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine.In certain aspects of the forty fourth embodiment, the inventionprovides a pharmaceutically acceptable salt of(3R,4R)-1-(4,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine.

In a forty fifth embodiment, the invention provides6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.In certain aspects of the forty fifth embodiment embodiment, theinvention provides a pharmaceutically acceptable salt of6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.

In a forty sixth embodiment, the invention provides(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.In certain aspects of the forty sixth embodiment, the invention providesa pharmaceutically acceptable salt of(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.The hydrochloride salt is a particularly preferred aspect of the fortysixth embodiment, e.g.,(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrilehydrochloride.

In a forty seventh embodiment, the invention provides(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.In certain aspects of the forty seventh embodiment, the inventionprovides a pharmaceutically acceptable salt of(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile.

In a forty eighth embodiment, the invention provides6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile.In certain aspects of the forty eighth embodiment, the inventionprovides a pharmaceutically acceptable salt of6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile.

In a forty ninth embodiment, the invention provides(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile.In certain aspects of the forty ninth embodiment, the invention providesa pharmaceutically acceptable salt of(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile.

In a fiftieth embodiment, the invention provides(3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine.In certain aspects of the fiftieth embodiment, the invention provides apharmaceutically acceptable salt of(3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine.

In a fifty first embodiment, the invention provides(3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine.In certain aspects of the fifty first embodiment, the invention providesa pharmaceutically acceptable salt of(3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine.

In a further aspect of each of the forty second to fifty firstembodiment, each of the compounds and pharmaceutically acceptable saltsprovided therein may be used in the preparation of a medicament for usein treating a disease mediated by TRPC6 activity. In certain aspects,the compounds provided in the forty second to fifty first embodiment, orpharmaceutically acceptable salt thereof, may be used in the manufactureof a medicament for the treatment of a disease or disorder selected fromnephrotic syndrome, minimal change disease, focal segmentalglomerulosclerosis, collapsing glomerulopathy, membranous nephropathy,membranoproliferative glomerulonephritis, IGA nephropathy, acute renalfailure, chronic renal failure, diabetic nephropathy, sepsis, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS), heart failure, stroke, malignant tumor or muscular dystrophy. Instill other aspects, the compounds of the forty second to fifty firstembodiment, or pharmaceutically acceptable salt thereof may be used inthe preparation of a medicament for the treatment of nephrotic syndrome,membranous nephropathy and acute renal failure.

In a fifty second embodiment, a method of treating disease or disorderin a patient in need of therapy is provided, the method comprises thestep of administering a pharmaceutically acceptable compositioncomprising a compound of any one of the forty second to fifty firstembodiments, or a pharmaceutically acceptable salt thereof, wherein thedisease or disorder is selected from nephrotic syndrome, minimal changedisease, focal segmental glomerulosclerosis, collapsing glomerulopathy,membranous nephropathy, membranoproliferative glomerulonephritis. IGAnephropathy, acute renal failure, chronic renal failure, diabeticnephropathy, sepsis, pulmonary hypertension, acute lung disorder, acuterespiratory distress syndrome (ARDS), heart failure, stroke, malignanttumor or muscular dystrophy. In certain aspects of the fifty firstembodiment the disease or disorder is selected from nephrotic syndrome,membranous nephropathy and acute renal failure.

In a further embodiment, the invention provides methods of making acompound of formula IIIb or a subformulae thereof.

The method comprising the synthetic steps of

(a) Alkylating a halogenated benzimidazole having the formula:

with an electrophilic moiety having the formula:

under basic conditions to provide an alkylated halogenated benzimidazolecompound having the formula:

wherein X is chlorine, bromine or iodine and Q is chlorine, bromine,iodine, C₁-C₆alkylsulfonate or optionally substituted phenylsulfonate;

(b) Coupling the alkylated halogenated benzimidazole generated in step(a) with a protected piperidine having the formula:

wherein PG is an amide protecting group stable to nucleophilic aromaticsubstitution (such as an alkoxycarbonyl protecting group) underconditions conducive to nucleophilic aromatic substitution to generatean alkylated 2-(piperidin-1-yl)benzimidazole compound having theformula:

and

(c) removing PG from the alkylated 2-(piperidin-1-yl)benzimidazolecompound formed in step (b) to generate the compound of Formula (IIIb),wherein variables X¹, X², X³. Z⁴, R^(1a), R², R³, R⁴, R⁷, R¹¹, R¹², R¹³and R¹⁵ have the definitions provided in the thirtieth embodiment

In preferred aspects of the synthetic method, the basic conditions ofstep (a) comprise contacting the halogenated benzimidazole with theelectrophilic moiety in the presence of a carbonate base, such aspotassium carbonate or more preferably cesium carbonate.

In a further embodiment, the invention provides methods of makingcompounds of formula IIb or a subformulae thereof.

The method comprising the synthetic steps of

(a) Coupling a halogenated benzimidazole having the formula:

with a protected piperidine having the formula:

under conditions conducive to nucleophilic aromatic substitution togenerate a 2-(piperidin-1-yl)benzimidazole compound having the formula:

wherein X is chlorine, bromine or iodine and PG is an amide protectinggroup stable to nucleophilic aromatic substitution such as analkoxycarbonyl protecting group;

(b) Alkylating the 2-(piperidin-1-yl)benzimidazole compound generated instep (a) with an

electrophilic moiety having the structure under basic conditions toprovide an alkylated 2-(piperidin-1-yl)benzimidazole compound having theformula:

wherein Q is chlorine, bromine, iodine, C₁-C₆alkylsulfonate oroptionally substituted phenylsulfonate:

(c) removing PG from the alkylated 2-(piperidin-1-yl)benzimidazolecompound generated in step (b) to generate the compound of Formula(IIIb), wherein variables X¹, X², X³, Z⁴, R^(1a), R², R³, R⁴, R⁷, R¹¹,R¹², R¹³ and R¹⁵ have the definitions provided in the thirtiethembodiment.

In a further embodiment, the invention provides methods of makingcompounds of formula IIIb or a subformulae thereof.

The method comprising the synthetic steps of

(a) Coupling a brominated isothiocyanate compound having the formula

with a protected piperidine compound having the formula:

under conditions conducive to thiourea formation to generate aN,N′-disubstituted thiourea compound having the formula

wherein PG is an amide protecting group such as an alkoxycarbonylprotecting group;

(b) Condensing the N,N′-disubstituted thiourea compound generated instep (a) with an amine compound having the formula

under conditions suitable to guanidine formation to provide aN,N′,N″-trisubstituted guanidine compound having the formula:

(c) Intramolecular cyclization of the N,N′,N″-trisubstituted guanidinecompound generated in step (b) in presence of a transition metalcatalyst to form an alkylated 2-(piperidin-1-yl)benzimidazole compoundhaving the formula:

(d) removing PG from the alkylated 2-(piperidin-1-yl)benzimidazolecompound generated in step (c) to provide a compound of Formula (IIIb),wherein variables X¹, X², X³, Z⁴, R^(1a), R², R³, R⁴, R⁷, R¹¹, R¹², R¹³and R¹⁵ have the definitions provided in the thirtieth embodiment.

In a further embodiment, the invention provides methods of makingcompounds of formula IIId or a subformulae thereof.

The method comprising the synthetic steps of

-   a) coupling an optionally substituted ortho-fluoro nitrobenzene    compound having the formula:

with a primary amine having the formula:

under conditions suitable for nucleophilic aromatic substitution toprovide a secondary amine amine having the formula:

-   b) generating an alkylated-2-chlorobenzimidazole compound having the    formula:

by reduction of the nitro substitutent in the secondary amine compoundsgenerated in step (a) to form in situ a dianiline compound, cyclizingsaid dianiline with a carbonyl source and clorination (with a chlorinesource such as e.g., P(O)Cl₃) to generate thealkylated-2-chlorobenzimidazole compound;

-   c) coupling the alkylated-2-chlorobenzimidazole compound generated    in step (b) with a protected piperidine having the formula:

under conditions suitable for nucleophilic aromatic substitution togenerate an alkylated 2-(piperidin-1-yl)benzimidazole compound havingthe formula:

-   d) removing the PG from the alkylated    2-(piperidin-1-yl)benzimidazole compound generated in step (c), to    generate the compound of Formula (IIId), wherein variables X¹, X²,    X³, R¹, R², R³, R⁴, R⁷. R¹¹, R¹², R¹³, R¹⁴ and R¹⁵ have the    definitions provided in the thirtieth embodiment.

In a further embodiment, the invention provides methods of makingcompounds of formula VII or a subformulae thereof.

-   (a) Coupling a halogenated benzimidazole having the formula:

with a protected piperidine having the formula R

under conditions conducive to nucleophilic aromatic substitution togenerate a 2-(piperidin-1-yl)benzimidazole compound having the formula

wherein X is chlorine, bromine or iodine and PG is an amide protectinggroup stable to nucleophilic aromatic substitution such as analkoxycarbonyl protecting group;

-   (b) Alkylating the 2-(piperidin-1-yl)benzimidazole compound    generated in step (a) with a halo ester,

wherein Y is X is chlorine, bromine or iodine and R is C₁-C₆alkyl, togenerate an substituted 1-acetyl-2-(piperidin-1-yl)benzimidazolecompound having the formula:

-   (c) Saponification of the substituted    1-acetyl-2-(piperidin-1-yl)benzimidazole compound generated in    step (b) to provide a free acid followed by amination with an amine,    HNR⁹R¹⁰, under conditions conducive to amide bond formation to    provide a 1-[(2-piperidin-1-yl)benzimidazole)]acetamide compound:-   (d) removing PG from the    1-[(2-piperidin-1-yl)benzimidazole)]acetamide compound generated in    step (c) to generate the compound of Formula (VII), wherein    variables X¹, X², X³, Z⁴, R^(1a), R², R³, R⁴, R⁷, R¹¹, R¹², R¹³ and    R¹⁵ have the definitions provided in the thirty fourth embodiment.

In another embodiment, pharmaceutical compositions are provided whichcomprise one or more pharmaceutically acceptable carriers and atherapeutically effective amount of a compound of any one of formulae Ior a subformulae thereof. In some aspects, the composition is formulatedin a form selected from the group consisting of an injectable fluid, anaerosol, a tablet, a pill, a capsule, a syrup, a cream, a gel and atransdermal patch.

In another embodiment, combinations, in particular pharmaceuticalcombinations, are provided which comprise a therapeutically effectiveamount of the compound any one of formulae I or a subformulae thereof.

In another embodiment, methods of modulating TRPC protein activity in asubject are provided which methods comprise administering to the subjecta therapeutically effective amount of Formula I or a subformulaethereof. In preferred aspects of the embodiment, methods of inhibitingTRPC6 activity in a subject are provided, which methods compriseadministering to the subject a therapeutically effective amount of acompound of Formula I or subformulae thereof. In certain aspects of theembodiment, method of inhibiting TRPC6 activity in a subject areprovided, which methods comprise administering to the subject atherapeutically effective amount of a compound of Formula I orsubformulae thereof.

In yet other embodiments, methods of treating a disorder or a disease ina subject mediated by TRPC protein activity are provided, in particularmethods of treating a disease or disorder mediated by TRPC6 proteinactivity are provided. The methods comprise administering to the subjecta therapeutically effective amount of the compound of Formula I or asubformulae thereof.

In another embodiment, methods of treating or preventing a disease ordisorder are provided where the disease or disorder is selected fromnephrotic syndrome, minimal change disease, focal segmentalglomerulosclerosis, collapsing glomerulopathy, membranous nephropathy,membranoproliferative glomerulonephritis, IGA nephropathy, acute renalfailure, chronic renal failure, diabetic nephropathy, sepsis, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS), heart failure, stroke, malignant tumor or muscular dystrophywhich method comprises the step of administering to a subject in need oftherapy a therapeutically effective amount of a compound or salt ofFormula I or a subformulae thereof. In certain aspects of thisembodiment, the method comprises treating a disease or disorder selectedfrom nephrotic syndrome, minimal change disease, focal segmentalglomerulosclerosis, collapsing glomerulopathy, membranous nephropathy,membranoproliferative glomerulonephritis, IGA nephropathy, acute renalfailure, chronic renal failure, diabetic nephropathy, sepsis, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS), heart failure, stroke, malignant tumor or muscular dystrophy. Incertain instances, the treatment methods and/or the prevention methodsare suitable for the treatment and or prevention nephrotic syndrome,membranous nephropathy, and acute renal failure.

In another aspect, the invention provides for the use of compounds ofFormula I or a subformulae thereof for use in the preparation of amedicament or for use in the manufacture of a medicament for thetreatment of a disorder or disease in a subject mediated by TRPC proteinactivity. In certain other aspects, the invention provides for the useof a compound according to formula I or a subformulae thereof in thetreatment of nephrotic syndrome, minimal change disease, focal segmentalglomerulosclerosis, collapsing glomerulopathy, membranous nephropathy,membranoproliferative glomerulonephritis. IGA nephropathy, acute renalfailure, chronic renal failure, diabetic nephropathy, sepsis, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS), heart failure, stroke, malignant tumor or muscular dystrophy. Incertain instances, the invention provides for the use of compounds ofFormula I or a subformulae thereof for use in the preparation of amedicament or for use in the manufacture of a medicament or thetreatment of a disease or disdorder in a subject selected from nephroticsyndrome, membranous nephropathy, and acute renal failure.

For purposes of interpreting this specification, the followingdefinitions will apply and whenever appropriate, terms used in thesingular will also include the plural and vice versa.

As used herein, the term “alkyl” refers to a fully saturated branched orunbranched hydrocarbon moiety having up to 20 carbon atoms. Unlessotherwise provided, alkyl refers to hydrocarbon moieties having 1 to 20carbon atoms, 1 to 16 carbon atoms, 1 to 10 carbon atoms, 1 to 7 carbonatoms, or 1 to 4 carbon atoms. Representative examples of alkyl include,but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl,sec-butyl, iso-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl,n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl,n-heptyl, n-octyl, n-nonyl, n-decyl and the like.

As used herein, the term “alkylene” refers to divalent alkyl group asdefined herein above having 1 to 20 carbon atoms. Unless otherwiseprovided, alkylene refers to moieties having 1 to 20 carbon atoms. 1 to16 carbon atoms. 1 to 10 carbon atoms. 1 to 7 carbon atoms, or 1 to 4carbon atoms. Representative examples of alkylene include, but are notlimited to, methylene, ethylene, n-propylene, iso-propylene, n-butylene,sec-butylene, iso-butylene, tert-butylene, n-pentylene, isopentylene,neopentylene, n-hexylene, 3-methylhexylene, 2,2-dimethylpentylene,2,3-dimethylpentylene, n-heptylene, n-octylene, n-nonylene, n-decyleneand the like.

As used herein, the term “haloalkyl” refers to an alkyl as definedherein, which is substituted with one or more halo groups as definedherein. The haloalkyl can be monohaloalkyl, dihaloalkyl or polyhaloalkylincluding perhaloalkyl. A monohaloalkyl can have one iodo, bromo, chloroor fluoro within the alkyl group. Dihaloalky and polyhaloalkyl groupscan have two or more of the same halo atoms or a combination ofdifferent halo groups within the alkyl. Typically the polyhaloalkylcontains up to 12, or 10, or 8, or 6, or 4, or 3, or 2 halo groups.Non-limiting examples of haloalkyl include fluoromethyl, difluoromethyl,trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl,pentafluoroethyl, heptafluoropropyl, difluorochloromethyl,dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl anddichloropropyl. A perhaloalkyl refers to an alkyl having all hydrogenatoms replaced with halo atoms.

As used herein, the term “hydroxy alkyl” refers to an alkyl as definedherein which is substituted with one or more hydroxy groups. The term“hydroxy cycloalkyl-alkyl” refers to an alkyl group that is substitutedwith a cycloalkyl group, as defined herein, and further substituted witha hydroxy group. The hydroxy group can be on the alkyl group, thecycloalkyl group, or on each of the alkyl and cycloalkyl groups.

The term “aryl” refers to an aromatic hydrocarbon group having 6-20carbon atoms in the ring portion. Typically, aryl is monocyclic,bicyclic or tricyclic aryl having 6-20 carbon atoms. Furthermore, theterm “aryl” as used herein, refers to an aromatic substituent which canbe a single aromatic ring, or multiple aromatic rings that are fusedtogether. Non-limiting examples include phenyl, naphthyl ortetrahydronaphthyl, each of which may optionally be substituted with 1-4substituents, such as alkyl, trifluoromethyl, cycloalkyl, halogen,hydroxy, alkoxy, acyl, alkyl-C(O)—O—, aryl-O—, heteroaryl-O—, amino,thiol, alkyl-S—, aryl-S-nitro, cyano, carboxy, alkyl-O—C(O)—, carbamoyl,alkyl-S(O)—, sulfonyl, sulfonamido, phenyl, and heterocyclyl.

As used herein, the term “heterocycle,” “heterocyclyl,”“heterocycloalkyl” or “heterocyclo” refers to a saturated or unsaturatednon-aromatic ring or ring system, e.g., which is a 4-, 5-, 6-, or7-membered monocyclic, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic or10-, 11-, 12-, 13-, 14- or 15-membered tricyclic ring system andcontains at least one heteroatom selected from O, S and N, where the Nand S can also optionally be oxidized to various oxidation states. Theheterocyclic group can be attached at a heteroatom or a carbon atom. Theheterocyclyl can include fused or bridged rings as well as spirocyclicrings. Examples of heterocycles include tetrahydrofuran, dihydrofuran,1,4-dioxane, morpholine, 1,4-dithiane, piperazine, piperidine.1,3-dioxolane, imidazolidine, imidazoline, pyrroline, pyrrolidine,tetrahydropyran, dihydropyran, oxathiolane, dithiolane, 1,3-dioxane,1,3-dithiane, oxathiane, thiomorpholine, azetidine, thiazolidine,morpholine, and the like.

As used herein, the term “azacycle” refers to a heterocycle whichcomprises at least one ring nitrogen atoms and which may optionallycomprise 0, 1 or 2 additional ring heteroatoms selected from N, O or S.

As used herein, the term “cycloalkyl” refers to saturated or partiallyunsaturated monocyclic, bicyclic or tricyclic hydrocarbon groups of 3-12carbon atoms. For the avoidance of doubt, cycloalkyl is not intended toinclude aromatic groups such as naphthylene or phenyl. Unless otherwiseprovided, cycloalkyl refers to cyclic hydrocarbon groups having between3 and 9 ring carbon atoms or between 3 and 7 ring carbon atoms, each ofwhich can be optionally substituted with one, or two, or three, or moresubstituents independently selected from the group consisting of alkyl,halo, oxo, hydroxy, alkoxy, alkyl-C(O)—, acylamino, carbamoyl,alkyl-NH—, (alkyl)₂N—, thiol, alkyl-S—, nitro, cyano, carboxy,alkyl-O—C(O)—, sulfonyl, sulfonamido, sulfamoyl, and heterocyclyl.Exemplary monocyclic hydrocarbon groups include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl andcyclohexenyl and the like. Exemplary bicyclic hydrocarbon groups includebornyl, indyl, hexahydroindyl, tetrahydronaphthyl, decahydronaphthyl,bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl,6,6-dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl,bicyclo[2.2.2]octyl and the like. Exemplary tricyclic hydrocarbon groupsinclude adamantyl and the like. The term “hydroxy cycloalkyl” refersspecifically to a cycloalkyl group substituted with one or more hydroxygroups.

As used herein, the term “alkoxy” refers to alkyl-O—, wherein alkyl isdefined herein above. Representative examples of alkoxy include, but arenot limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy,tert-butoxy, pentyloxy, hexyloxy, cyclopropyloxy-, cyclohexyloxy- andthe like. Typically, alkoxy groups have about 1-7, more preferably about1-4 carbons.

As used herein, the term “cycloalkoxy” refers to cycloalkyl-O— andcycloalkyl-alkyl-O, wherein cycloalkyl and alkyl are defined hereinabove. Representative examples of cycloalkoxy include, but are notlimited to, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy,1-methylcyclopropyloxy, cyclopropylmethoxy. 1-methylcyclobutyloxy andthe like. Typically, cycloalkoxy groups have about 3-7, more preferablyabout 3-6 carbon atoms.

Divalent substituents are represented with a “diyl” suffix. Thus adivalent alkyl linker is referred to as an alkandiyl group and adivalent cycloalkane group is referred to as a cycloalkandiyl (e.g.,cyclopropandiyl).

As used herein, the term “heteroaryl” refers to a 5-14 memberedmonocyclic- or bicyclic- or tricyclic-aromatic ring system, having 1 to8 heteroatoms selected from N, O and S. In certain preferred aspects,the heteroaryl is a 5-10 membered ring system (e.g., 5-7 memberedmonocycle or an 8-10 membered bicycle) or a 5-7 membered ring system.Exemplary monocyclic heteroaryl groups include 2- or 3-thienyl. 2- or3-furyl, 2- or 3-pyrrolyl, 2-, 4-, or 5-imidazolyl. 3-, 4-, or5-pyrazolyl. 2-, 4-, or 5-thiazolyl. 3-, 4-, or 5-isothiazolyl. 2-, 4-,or 5-oxazolyl, 3-, 4-, or 5-isoxazolyl, 3- or 5-1,2,4-triazolyl, 4- or5-1,2,3-triazolyl, tetrazolyl, 2-, 3-, or 4-pyridyl, 3- or4-pyridazinyl, 3-, 4-, or 5-pyrazinyl, 2-pyrazinyl, and 2-, 4-, and5-pyrimidinyl. Exemplary bicyclic heteroaryl groups include 1-, 3-, 4-,5-, 6-, 7-, or 8-isoquinolinyl. 2-3-, 4-, 5-, 6-, 7-, or 8-quinolinyl.1-, 3-, 4-, 5-, 6-, 7-, or 8-isoquinolinyl, 1-, 2-, 4-, 5-, 6-, 7-, or8-benzimidazolyl and 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-indolyl.

The term “heteroaryl” also refers to a group in which a heteroaromaticring is fused to one or more aryl, cycloaliphatic, or heterocyclylrings, where the radical or point of attachment is on the heteroaromaticring.

The terms “bicycle” and “bicyclyl” refers to a ring system having twofused rings each of which rings may be carbocyclic or heterocyclic andeach of which rings may be saturated, unsaturated or aromatic.

As used herein, the term “halogen” or “halo” refers to fluoro, chloro,bromo, and iodo.

As used herein, the term “optionally substituted” unless otherwisespecified refers to a group that is unsubstituted or is substituted withone or more, typically 1, 2, 3 or 4, suitable non-hydrogen substituents.If the identity of the “optional substituent” is not clearly defined incontext of the optionally substituted group, then each optionalsubstituent is independently selected from the group consisting of:alkyl, hydroxy, halogen, oxo, amino, alkylamino, dialkylamino, alkoxy,cycloalkyl, CO₂H, heterocycloalkyloxy (which denotes a heterocyclicgroup bonded through an oxygen bridge), —CO₂alkyl, mercapto, nitro,cyano, sulfamoyl, sulfonamide, aryl, —OC(O)alkyl, —OC(O)aryl, aryl-S—,aryloxy; alkylthio, formyl (i.e., HC(O)—). —C(O)NH₂, aralkyl (alkylsubstituted with aryl), aryl and aryl substituted with alkyl,cycloalkyl, alkoxy, hydroxy, amino, alkyl-C(O)—NH—, alkylamino,dialkylamino or halogen. It is understood that where a group isindicated to be optionally substituted, the disclosure includesembodiments in which the group is unsubstituted as well as embodimentsin which the group is substituted.

As used herein, the term “isomers” refers to different compounds thathave the same molecular formula but differ in arrangement andconfiguration of the atoms. Also as used herein, the term “an opticalisomer” or “a stereoisomer” refers to any of the various stereo isomericconfigurations which may exist for a given compound of the presentinvention and includes geometric isomers. It is understood that asubstituent may be attached at a chiral center of a carbon atom.Therefore, the invention includes enantiomers, diastereomers orracemates of the compound. “Enantiomers” are a pair of stereoisomersthat are non-superimposable mirror images of each other. A 1:1 mixtureof a pair of enantiomers is a “racemic” mixture. The term is used todesignate a racemic mixture where appropriate. The use of “rel”indicates that the diastereomeric orientation is known but the absolutestereochemistry is not. In cases where the absolute stereochemistry hasnot been determined the optical rotation and/or chiral chromatographyconditions will indicate which isomer is present.

“Diastereoisomers” are stereoisomers that have at least two asymmetricatoms, but which are not mirror-images of each other. The absolutestereochemistry is specified according to the Cahn-Ingold-Prelog R-Ssystem. When a compound is a pure enantiomer the stereochemistry at eachchiral carbon may be specified by either R or S. Resolved compoundswhose absolute configuration is unknown can be designated (+) or (−)depending on the direction (dextro- or levorotatory) which they rotateplane polarized light at the wavelength of the sodium D line orretention time on chiral chromatography separation. Certain of thecompounds described herein contain one or more asymmetric centers oraxes and may thus give rise to enantiomers, diastereomers, and otherstereoisomeric forms that may be defined, in terms of absolutestereochemistry, as (R)- or (S)-, or with the (+) or (−) sign. Thepresent invention is meant to include all such possible isomers,including racemic mixtures, optically pure forms and intermediatemixtures. Optically active (R)- and (S)-isomers may be prepared usingchiral synthons or chiral reagents, or resolved using conventionaltechniques. If the compound contains a double bond, the substituent maybe E or Z configuration. If the compound contains a disubstitutedcycloalkyl, the cycloalkyl substituent may have a cis- ortrans-configuration.

It is understood that for any compound provided herein, including anycompound of Formula (I), or any embodiment thereof, or any compound ofTable A, B, or C, or a salt of any of the foregoing, the compound mayexist in any stereochemical form, such as a single enantiomer,diastereomer, or tautomer or a mixture of one or more enantiomers,diastereomers, and tautomers in any ratio.

As used herein, the terms “salt” or “salts” refers to an acid additionor base addition salt of a compound of the invention. “Salts” include inparticular “pharmaceutical acceptable salts”. The term “pharmaceuticallyacceptable salts” refers to salts that retain the biologicaleffectiveness and properties of the compounds of this invention and,which typically are not biologically or otherwise undesirable. In manycases, the compounds of the present invention are capable of formingacid and/or base salts by virtue of the presence of amino and/orcarboxyl groups or groups similar thereto.

Pharmaceutically acceptable acid addition salts can be formed withinorganic acids and organic acids.

Inorganic acids from which salts can be derived include, for example,hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like.

Organic acids from which salts can be derived include, for example,acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid,malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid,benzoic acid, mandelic acid methanesulfonic acid, ethanesulfonic acidbenzenesuflonic acid, toluenesulfonic acid, sulfosalicylic acid, and thelike.

Pharmaceutically acceptable base addition salts can be formed withinorganic and organic bases.

Inorganic bases from which salts can be derived include, for example,ammonium salts and metals from columns I to XII of the periodic table.In certain embodiments, the salts are derived from sodium, potassium,ammonium, calcium, magnesium, iron, silver, zinc, and copper. In certainother embodiments, the salts are selected from ammonium, potassium,sodium, calcium and magnesium salts.

Organic bases from which salts can be derived include, for example,primary, secondary, and tertiary amines, substituted amines includingnaturally occurring substituted amines, cyclic amines, basic ionexchange resins, and the like. Certain organic amines includeisopropylamine, benzathine, cholinate, diethanolamine, diethylamine,lysine, meglumine, piperazine and tromethamine.

In another aspect, the present invention provides compounds as disclosedherein in acetate, ascorbate, adipate, aspartate, benzoate, besylate,bromide/hydrobromide, bicarbonate/carbonate, bisulfate/sulfate,camphorsulfonate, caprate, chloride/hydrochloride, chlortheophyllonate,citrate, ethandisulfonate, fumarate, gluceptate, gluconate, glucuronate,glutamate, glutarate, glycolate, hippurate, hydroiodide/iodide,isethionate, lactate, lactobionate, laurylsulfate, malate, maleate,malonate, mandelate, mesylate, methylsulphate, mucate, naphthoate,napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate,palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate,polygalacturonate, propionate, sebacate, stearate, succinate,sulfosalicylate, sulfate, tartrate, tosylate trifenatate,trifluoroacetate or xinafoate salt form. In yet another aspect, thepresent invention provides compounds as disclosed herein in C₁-C₄alkylsufonic acid, benzenesulfonic acid or mono-, di- or tri-C₁-C₄alklsubstituted benzene sulfonic acid addition salt form.

Any formula given herein is also intended to represent unlabeled formsas well as isotopically labeled forms of the compounds. Isotopicallylabeled compounds have structures depicted by the formulas given hereinexcept that one or more atoms are replaced by an atom having a selectedatomic mass or mass number. Examples of isotopes that can beincorporated into compounds of the invention include isotopes ofhydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, and chlorine,such as ²H, ³H, ¹¹C, ¹³C, ¹⁴C, ¹⁵N, ¹⁸F ³¹P, ³²P, ³⁵S, ³⁶Cl, ¹²⁴, ¹²⁵Irespectively. The invention includes various isotopically labeledcompounds as defined herein, for example those into which radioactiveisotopes, such as ³H, ¹³C, and ¹⁴C, are present. Such isotopicallylabelled compounds are useful in metabolic studies (with ¹⁴C), reactionkinetic studies (with, for example ²H or ³H), detection or imagingtechniques, such as positron emission tomography (PET) or single-photonemission computed tomography (SPECT) including drug or substrate tissuedistribution assays, or in radioactive treatment of patients. Inparticular, an ¹⁸F or labeled compound may be particularly desirable forPET or SPECT studies. Isotopically labeled compounds of this inventionand salts thereof can generally be prepared by carrying out theprocedures disclosed in the schemes or in the examples and preparationsdescribed below by substituting a readily available isotopically labeledreagent for a non-isotopically labeled reagent.

Further, substitution with heavier isotopes, particularly deuterium(i.e., ²H or D) may afford certain therapeutic advantages resulting fromgreater metabolic stability, for example increased in vivo half-life orreduced dosage requirements or an improvement in therapeutic index. Itis understood that deuterium in this context is regarded as asubstituent of a compound of the formula (I). The concentration of sucha heavier isotope, specifically deuterium, may be defined by theisotopic enrichment factor. The term “isotopic enrichment factor” asused herein means the ratio between the isotopic abundance and thenatural abundance of a specified isotope. If a substituent in a compoundof this invention is denoted deuterium, such compound has at least 50%deuterium incorporation at each designated deuterium atom, 60% deuteriumincorporation, at least 75% deuterium incorporation, at least 90%deuterium incorporation, at least 95% deuterium incorporation, at least99% deuterium incorporation, or at least 99.5% deuterium incorporation.

The compounds of the present invention may inherently or by design formsolvates with solvents (including water). Therefore, it is intended thatthe invention embrace both solvated and unsolvated forms. The term“solvate” refers to a molecular complex of a compound of the presentinvention (including salts thereof) with one or more solvent molecules.Such solvent molecules are those commonly used in the pharmaceuticalart, which are known to be innocuous to a recipient, e.g., water,ethanol, dimethylsulfoxide, acetone and other common organic solvents.The term “hydrate” refers to a molecular complex comprising a compoundof the invention and water. Pharmaceutically acceptable solvates inaccordance with the invention include those wherein the solvent ofcrystallization may be isotopically substituted, e.g. D₂O, d₆-acetone,d₆-DMSO.

The term “a therapeutically effective amount” of a compound of thepresent invention refers to an amount of the compound of the presentinvention that will elicit the biological or medical response of asubject, for example, reduction or inhibition of an enzyme or a proteinactivity, or ameliorate symptoms, alleviate conditions, slow or delaydisease progression, or prevent a disease, etc. In one non-limitingembodiment, the term “a therapeutically effective amount” refers to theamount of the compound of the present invention that, when administeredto a subject, is effective to (1) at least partially alleviating,inhibiting, preventing and/or ameliorating a condition, or a disorder,or a disease or biological process (i) mediated by TRPC6 activity, or(ii) associated with TRPC6 activity; or (2) inhibiting the activity ofTRPC6. In another non-limiting embodiment, the term “a therapeuticallyeffective amount” refers to the amount of the compound of the presentinvention that, when administered to a cell, or a tissue, or anon-cellular biological material, or a medium, is effective to at leastpartially inhibit TRPC6 activity.

As used herein, the term “subject” refers to an animal. Typically theanimal is a mammal. A subject also refers to for example, primates(e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats,mice, fish, birds and the like. In certain embodiments, the subject is aprimate. In yet other embodiments, the subject is a human.

As used herein, the term “inhibit”, “inhibition” or “inhibiting” refersto the reduction or suppression of a given condition, symptom, ordisorder, or disease, or a significant decrease in the baseline activityof a biological activity or process.

As used herein, the term “treat”, “treating” or “treatment” of anydisease or disorder refers in one embodiment, to ameliorating thedisease or disorder (i.e., slowing or arresting or reducing thedevelopment of the disease or at least one of the clinical symptomsthereof). In another embodiment “treat”, “treating” or “treatment”refers to alleviating or ameliorating at least one physical parameterincluding those which may not be discernible by the patient. In yetanother embodiment, “treat”, “treating” or “treatment” refers tomodulating the disease or disorder, either physically, (e.g.,stabilization of a discernible symptom), physiologically, (e.g.,stabilization of a physical parameter), or both.

As used herein, the term “prevent,” “preventing” or “prevention” of anydisease or disorder refers in one embodiment, to delay or avoidance ofonset of the disease or disorder (i.e., slowing or preventing the onsetof the disease or disorder in a patient susceptible to development ofthe disease or disorder).

As used herein, a subject is “in need of” a treatment if such subjectwould benefit biologically, medically or in quality of life from suchtreatment.

As used herein, the term “a,” “an,” “the” and similar terms used in thecontext of the present invention (especially in the context of theclaims) are to be construed to cover both the singular and plural unlessotherwise indicated herein or clearly contradicted by the context.

Any asymmetric atom (e.g., carbon or the like) of the compound(s) of thepresent invention can be present in racemic or enantiomericallyenriched, for example the (R)-, (S)- or (R,S)-configuration. In certainembodiments, each asymmetric atom has at least 50% enantiomeric excess,at least 60% enantiomeric excess, at least 70% enantiomeric excess, atleast 80% enantiomeric excess, at least 90% enantiomeric excess, atleast 95% enantiomeric excess, or at least 99% enantiomeric excess inthe (R)- or (S)-configuration. Substituents at atoms with unsaturatedbonds may, if possible, be present in cis-(Z)- or trans-(E)-form.

Accordingly, as used herein a compound of the present invention can bein the form of one of the possible isomers, rotamers, atropisomers,tautomers or mixtures thereof, for example, as substantially puregeometric (cis or trans) isomers, diastereomers, optical isomers(antipodes), racemates or mixtures thereof.

Any resulting mixtures of isomers can be separated on the basis of thephysicochemical differences of the constituents, into the pure orsubstantially pure geometric or optical isomers, diastereomers,racemates, for example, by chromatography and/or fractionalcrystallization.

Any resulting racemates of final products or intermediates can beresolved into the optical antipodes by known methods. e.g., byseparation of the diastereomeric salts thereof, obtained with anoptically active acid or base, and liberating the optically activeacidic or basic compound. In particular, a basic moiety may thus beemployed to resolve the compounds of the present invention into theiroptical antipodes, e.g., by fractional crystallization of a salt formedwith an optically active acid, e.g., tartaric acid, dibenzoyl tartaricacid, diacetyl tartaric acid, di-O,O′-p-toluoyl tartaric acid, mandelicacid, malic acid or camphor-10-sulfonic acid. Racemic products can alsobe resolved by chiral chromatography, e.g., high performance liquidchromatography (HPLC) or supercritical fluid chromatography (SFC) usinga chiral adsorbent.

Mixtures of isomers obtainable according to the invention can beseparated in a manner known to those skilled in the art into theindividual isomers; diastereoisomers can be separated, for example, bypartitioning between polyphasic solvent mixtures, recrystallizationand/or chromatographic separation, for example over silica gel or bye.g. medium pressure liquid chromatography over a reversed phase column,and racemates can be separated, for example, by the formation of saltswith optically pure salt-forming reagents and separation of the mixtureof diastereoisomers so obtainable, for example by means of fractionalcrystallization, or by chromatography over optically active columnmaterials.

Within the scope of this text, only a readily removable group that isnot a constituent of the particular desired end product of the compoundsof the present invention is designated a “protecting group”, unless thecontext indicates otherwise. The protection of functional groups by suchprotecting groups, the protecting groups themselves, and their cleavagereactions are described for example in standard reference works, such asJ. F. W. McOmie, “Protective Groups in Organic Chemistry”, Plenum Press.London and New York 1973, in T. W. Greene and P. G. M. Wuts. “ProtectiveGroups in Organic Synthesis”. Third edition. Wiley, New York 1999, in“The Peptides”; Volume 3 (editors: E. Gross and J. Meienhofer), AcademicPress, London and New York 1981, in “Methoden der organischen Chemie”(Methods of Organic Chemistry), Houben Weyl, 4th edition. Volume 15/I,Georg Thieme Verlag. Stuttgart 1974, in H.-D. Jakubke and H. Jeschkeit.“Aminosauren, Peptide, Proteine” (Amino acids. Peptides, Proteins),Verlag Chemie, Weinheim, Deerfield Beach, and Basel 1982, and in JochenLehmann. “Chemie der Kohlenhydrate: Monosaccharide and Derivate”(Chemistry of Carbohydrates: Monosaccharides and Derivatives), GeorgThieme Verlag, Stuttgart 1974. A characteristic of protecting groups isthat they can be removed readily (i.e. without the occurrence ofundesired secondary reactions) for example by solvolysis, reduction,photolysis or alternatively under physiological conditions (e.g. byenzymatic cleavage).

Intermediates and final products can be worked up and/or purifiedaccording to standard methods, e.g. using chromatographic methods,distribution methods, (re-) crystallization, and the like.

All methods described herein can be performed in any suitable orderunless otherwise indicated herein or otherwise clearly contradicted bycontext. The use of any and all examples, or exemplary language (e.g.“such as”) provided herein is intended merely to better illuminate theinvention and does not pose a limitation on the scope of the inventionotherwise claimed.

Any process steps disclosed herein can be carried out under reactionconditions that are known to those skilled in the art, including thosementioned specifically, in the absence or, customarily, in the presenceof solvents or diluents, including, for example, solvents or diluentsthat are inert towards the reagents used and dissolve them, in theabsence or presence of catalysts, condensation or neutralizing agents,for example ion exchangers, such as cation exchangers, e.g. in the H⁺form, depending on the nature of the reaction and/or of the reactants atreduced, normal or elevated temperature, for example in a temperaturerange of from about −100° C., to about 250° C., including, for example,from approximately −80° C., to approximately 250° C., for example atfrom −80 to −60° C., at room temperature, at from −20 to 40° C., or atreflux temperature, under atmospheric pressure or in a closed vessel,where appropriate under pressure, and/or in an inert atmosphere, forexample under an argon or nitrogen atmosphere.

The solvents from which those solvents that are suitable for anyparticular reaction may be selected include those mentioned specificallyor, for example, water, esters, such as lower alkyl-lower alkanoates,for example ethyl acetate, ethers, such as aliphatic ethers, for examplediethyl ether, or cyclic ethers, for example tetrahydrofuran or dioxane,liquid aromatic hydrocarbons, such as benzene or toluene, alcohols, suchas methanol, ethanol or 1- or 2-propanol, nitriles, such asacetonitrile, halogenated hydrocarbons, such as methylene chloride orchloroform, acid amides, such as dimethylformamide or dimethylacetamide, bases, such as heterocyclic nitrogen bases, for examplepyridine or N-methylpyrrolidin-2-one, carboxylic acid anhydrides, suchas lower alkanoic acid anhydrides, for example acetic anhydride, cyclic,linear or branched hydrocarbons, such as cyclohexane, hexane orisopentane, methycyclohexane, or mixtures of those solvents, for exampleaqueous solutions, unless otherwise indicated in the description of theprocesses. Such solvent mixtures may also be used in working up, forexample by chromatography or partitioning.

In another aspect, the present invention provides a pharmaceuticalcomposition comprising a compound of the present invention, or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable carrier. In a further embodiment, the composition comprisesat least two pharmaceutically acceptable carriers, such as thosedescribed herein. For purposes of the present invention, unlessdesignated otherwise, solvates and hydrates are generally consideredcompositions. Preferably, pharmaceutically acceptable carriers aresterile. The pharmaceutical composition can be formulated for particularroutes of administration such as oral administration, parenteraladministration, and rectal administration, etc. In addition, thepharmaceutical compositions of the present invention can be made up in asolid form (including without limitation capsules, tablets, pills,granules, powders or suppositories), or in a liquid form (includingwithout limitation solutions, suspensions or emulsions). Thepharmaceutical compositions can be subjected to conventionalpharmaceutical operations such as sterilization and/or can containconventional inert diluents, lubricating agents, or buffering agents, aswell as adjuvants, such as preservatives, stabilizers, wetting agents,emulsifiers and buffers, etc.

As used herein, the term “pharmaceutically acceptable carrier” includesany and all solvents, dispersion media, coatings, surfactants,antioxidants, preservatives (e.g., antibacterial agents, antifungalagents), isotonic agents, absorption delaying agents, salts,preservatives, drugs, drug stabilizers, binders, excipients,disintegration agents, lubricants, sweetening agents, flavoring agents,dyes, and the like and combinations thereof, as would be known to thoseskilled in the art (see, for example. Remington's PharmaceuticalSciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329). Exceptinsofar as any conventional carrier is incompatible with the activeingredient, its use in the therapeutic or pharmaceutical compositions iscontemplated.

Typically, the pharmaceutical compositions are tablets or gelatincapsules comprising the active ingredient together with one or more of:a) diluents, e.g., lactose, dextrose, sucrose, mannitol, sorbitol,cellulose and/or glycine: b) lubricants, e.g., silica, talcum, stearicacid, its magnesium or calcium salt and/or polyethyleneglycol; fortablets also c) binders, e.g., magnesium aluminum silicate, starchpaste, gelatin, tragacanth, methylcellulose, sodiumcarboxymethylcellulose and/or polyvinylpyrrolidone; if desired d)disintegrants, e.g., starches, agar, alginic acid or its sodium salt, oreffervescent mixtures; and e) absorbents, colorants, flavors andsweeteners. Tablets may be either film coated or enteric coatedaccording to methods known in the art. Suitable compositions for oraladministration include an effective amount of a compound of theinvention in the form of tablets, lozenges, aqueous or oily suspensions,dispersible powders or granules, emulsion, hard or soft capsules, orsyrups or elixirs. Compositions intended for oral use are preparedaccording to any method known in the art for the manufacture ofpharmaceutical compositions and such compositions can contain one ormore agents selected from the group consisting of sweetening agents,flavoring agents, coloring agents and preserving agents in order toprovide pharmaceutically elegant and palatable preparations. Tablets maycontain the active ingredient in admixture with nontoxicpharmaceutically acceptable excipients which are suitable for themanufacture of tablets. These excipients are, for example, inertdiluents, such as calcium carbonate, sodium carbonate, lactose, calciumphosphate or sodium phosphate: granulating and disintegrating agents,for example, corn starch, or alginic acid; binding agents, for example,starch, gelatin or acacia; and lubricating agents, for example magnesiumstearate, stearic acid or talc. The tablets are uncoated or coated byknown techniques to delay disintegration and absorption in thegastrointestinal tract and thereby provide a sustained action over alonger period. For example, a time delay material such as glycerylmonostearate or glyceryl distearate can be employed. Formulations fororal use can be presented as hard gelatin capsules wherein the activeingredient is mixed with an inert solid diluent, for example, calciumcarbonate, calcium phosphate or kaolin, or as soft gelatin capsuleswherein the active ingredient is mixed with water or an oil medium, forexample, peanut oil, liquid paraffin or olive oil. Certain injectablecompositions are aqueous isotonic solutions or suspensions, andsuppositories are advantageously prepared from fatty emulsions orsuspensions. Said compositions may be sterilized and/or containadjuvants, such as preserving, stabilizing, wetting or emulsifyingagents, solution promoters, salts for regulating the osmotic pressureand/or buffers. In addition, they may also contain other therapeuticallyvaluable substances. Said compositions are prepared according toconventional mixing, granulating or coating methods, respectively, andcontain about 0.1-75%, or contain about 1-50%, of the active ingredient.Suitable compositions for transdermal application include an effectiveamount of a compound of the invention with a suitable carrier. Carrierssuitable for transdermal delivery include absorbable pharmacologicallyacceptable solvents to assist passage through the skin of the host. Forexample, transdermal devices are in the form of a bandage comprising abacking member, a reservoir containing the compound optionally withcarriers, optionally a rate controlling barrier to deliver the compoundof the skin of the host at a controlled and predetermined rate over aprolonged period of time, and means to secure the device to the skin.Suitable compositions for topical application, e.g., to the skin andeyes, include aqueous solutions, suspensions, ointments, creams, gels orsprayable formulations. e.g., for delivery by aerosol or the like. Suchtopical delivery systems will in particular be appropriate for dermalapplication, e.g., for the treatment of skin cancer, e.g., forprophylactic use in sun creams, lotions, sprays and the like. They arethus particularly suited for use in topical, including cosmetic,formulations well-known in the art. Such may contain solubilizers,stabilizers, tonicity enhancing agents, buffers and preservatives. Asused herein a topical application may also pertain to an inhalation orto an intranasal application. They may be conveniently delivered in theform of a dry powder (either alone, as a mixture, for example a dryblend with lactose, or a mixed component particle, for example withphospholipids) from a dry powder inhaler or an aerosol spraypresentation from a pressurized container, pump, spray, atomizer ornebulizer, with or without the use of a suitable propellant.

The present invention further provides anhydrous pharmaceuticalcompositions and dosage forms comprising the compounds of the presentinvention as active ingredients, since water may facilitate thedegradation of certain compounds.

Anhydrous pharmaceutical compositions and dosage forms of the inventioncan be prepared using anhydrous or low moisture containing ingredientsand low moisture or low humidity conditions. An anhydrous pharmaceuticalcomposition may be prepared and stored such that its anhydrous nature ismaintained. Accordingly, anhydrous compositions are packaged usingmaterials known to prevent exposure to water such that they can beincluded in suitable formulary kits. Examples of suitable packaginginclude, but are not limited to, hermetically sealed foils, plastics,unit dose containers (e.g., vials), blister packs, and strip packs.

The invention further provides pharmaceutical compositions and dosageforms that comprise one or more agents that reduce the rate by which thecompound of the present invention as an active ingredient willdecompose. Such agents, which are referred to herein as “stabilizers,”include, but are not limited to, antioxidants such as ascorbic acid, pHbuffers, or salt buffers, etc.

Prophylactic and Therapeutic Uses

The compounds disclosed herein in free form or in pharmaceuticallyacceptable salt form, exhibit valuable pharmacological properties, e.g.TRPC protein modulating properties and more particularly inhibition ofTRPC6 protein activity. e.g. as indicated in in vitro and in vivo testsas provided in the next sections and are therefore indicated fortherapy.

The present invention provides methods of treating a disease or disorderassociated with TRPC6 protein activity by administering to a subject inneed thereof an effective amount of a compound disclosed herein. Incertain aspects, the disease or disorder suitable for therapy byadministration of the compound of the invention include, but are notlimited to, nephrotic syndrome, minimal change disease, focal segmentalglomerulosclerosis, collapsing glomerulopathy, membranous nephropathy,membranoproliferative glomerulonephritis, IGA nephropathy, acute renalfailure, chronic renal failure, diabetic nephropathy, sepsis, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS), heart failure, stroke, malignant tumor or muscular dystrophy. Incertain instances, the patient is suffering from nephrotic syndrome,membranous nephropathy, and acute renal failure.

In a specific embodiment, the present invention provides a method oftreating or preventing renal disease by administering to a subject inneed thereof an effective amount of a compound disclosed herein. Incertain embodiments, patients who are currently asymptomatic but are atrisk of developing renal disease are suitable for administration with acompound of the invention. The methods of treating or preventing renaldisease include, but are not limited to, methods of treating orpreventing nephrotic syndrome, membranous nephropathy, acute renalfailure, sepsis, chronic renal failure and diabetic nephropathy.

The pharmaceutical composition or combination of the present inventioncan be in unit dosage of about 1-1000 mg of active ingredient(s) for asubject of about 50-70 kg, or about 1-500 mg or about 1-250 mg or about1-150 mg or about 0.5-100 mg, or about 1-50 mg of active ingredients.The therapeutically effective dosage of a compound, the pharmaceuticalcomposition, or the combinations thereof, is dependent on the species ofthe subject, the body weight, age and individual condition, the disorderor disease or the severity thereof being treated. A physician, clinicianor veterinarian of ordinary skill can readily determine the effectiveamount of each of the active ingredients necessary to prevent, treat orinhibit the progress of the disorder or disease.

The above-cited dosage properties are demonstrable in vitro and in vivotests using advantageously mammals. e.g., mice, rats, dogs, monkeys orisolated organs, tissues and preparations thereof. The compounds of thepresent invention can be applied in vitro in the form of solutions,e.g., aqueous solutions, and in vivo either enterally, parenterally,advantageously intravenously, e.g., as a suspension or in aqueoussolution. The dosage in vitro may range between about 10⁻³ molar and10⁻⁹ molar concentrations. A therapeutically effective amount in vivomay range depending on the route of administration, between about0.1-500 mg/kg, or between about 1-100 mg/kg.

The activity of a compound according to the present invention can beassessed by in vitro & in vivo methods, such as those described in theexamples below.

The compound of the present invention may be administered eithersimultaneously with, or before or after, one or more other therapeuticagent. The compound of the present invention may be administeredseparately, by the same or different route of administration, ortogether in the same pharmaceutical composition as the other agents.

In one embodiment, the invention provides a product comprising acompound disclosed herein and at least one other therapeutic agent as acombined preparation for simultaneous, separate or sequential use intherapy. In one embodiment, the therapy is the treatment of a disease orcondition mediated by TRPC protein activity. In preferred aspects, thetherapy is a treatment for nephrotic syndrome, minimal change disease,focal segmental glomerulosclerosis, collapsing glomerulopathy,membranous nephropathy, membranoproliferative glomerulonephritis, IGAnephropathy, acute renal failure, chronic renal failure, diabeticnephropathy, sepsis, pulmonary hypertension, acute lung disorder, acuterespiratory distress syndrome (ARDS), heart failure, stroke, malignanttumor, or muscular dystrophy.

Products provided as a combined preparation include a compositioncomprising the compound disclosed herein and the other therapeuticagent(s) together in the same pharmaceutical composition, or thecompound disclosed herein and the other therapeutic agent(s) in separateform. e.g. in the form of a kit.

In one embodiment, the invention provides a pharmaceutical compositioncomprising a compound as disclosed herein and another therapeuticagent(s). Optionally, the pharmaceutical composition may comprise apharmaceutically acceptable carrier, as described above.

In one embodiment, the invention provides a kit comprising two or moreseparate pharmaceutical compositions, at least one of which contains acompound disclosed herein. In one embodiment, the kit comprises meansfor separately retaining said compositions, such as a container, dividedbottle, or divided foil packet. An example of such a kit is a blisterpack, as typically used for the packaging of tablets, capsules and thelike.

The kit of the invention may be used for administering different dosageforms, for example, oral and parenteral, for administering the separatecompositions at different dosage intervals, or for titrating theseparate compositions against one another. To assist compliance, the kitof the invention typically comprises directions for administration.

In the combination therapies of the invention, the compound of theinvention and the other therapeutic agent may be manufactured and/orformulated by the same or different manufacturers. Moreover, thecompound of the invention and the other therapeutic may be broughttogether into a combination therapy: (i) prior to release of thecombination product to physicians (e.g. in the case of a kit comprisingthe compound of the invention and the other therapeutic agent); (ii) bythe physician themselves (or under the guidance of the physician)shortly before administration; (iii) in the patient themselves. e.g.during sequential administration of the compound of the invention andthe other therapeutic agent.

Accordingly, the invention provides the use of a compound as disclosedherein for treating a disease or condition mediated by TRPC proteinactivity wherein the medicament is prepared for administration withanother therapeutic agent. The invention also provides the use ofanother therapeutic agent for treating a disease or condition mediatedby the TRPC protein activity, wherein the medicament is administeredwith a compound as disclosed herein. In another aspect, the inventionprovides the use of a compound as disclosed herein for treating adisease or disorder selected from nephrotic syndrome, minimal changedisease, focal segmental glomerulosclerosis, collapsing glomerulopathy,membranous nephropathy, membranoproliferative glomerulonephritis, IGAnephropathy, acute renal failure, chronic renal failure, diabeticnephropathy, sepsis, pulmonary hypertension, acute lung disorder, acuterespiratory distress syndrome (ARDS), heart failure, stroke, malignanttumor, or muscular dystrophy wherein the medicament is prepared foradministration with another therapeutic agent. The invention alsoprovides the use of another therapeutic agent for treating a disease ordisorder selected from nephrotic syndrome, minimal change disease, focalsegmental glomerulosclerosis, collapsing glomerulopathy, membranousnephropathy, membranoproliferative glomerulonephritis, IGA nephropathy,acute renal failure, chronic renal failure, diabetic nephropathy,sepsis, pulmonary hypertension, acute lung disorder, acute respiratorydistress syndrome (ARDS), heart failure, stroke, malignant tumor, ormuscular dystrophy, wherein the medicament is administered with acompound as disclosed herein.

The invention also provides a compound as disclosed herein for use in amethod of treating a disease or condition mediated by TRPC proteinactivity wherein the compound is prepared for administration withanother therapeutic agent. The invention also provides anothertherapeutic agent for use in a method of treating a disease or conditionmediated by TRPC protein activity, wherein the other therapeutic agentis prepared for administration with a compound as disclosed herein. Theinvention also provides a compound as disclosed herein for use in amethod of treating a disease or condition mediated by TRPC proteinactivity, wherein the compound is administered with another therapeuticagent. The invention also provides another therapeutic agent for use ina method of treating a disease or condition mediated by TRPC proteinactivity, wherein the other therapeutic agent is administered with acompound as disclosed herein.

The invention also provides the use of a compound as disclosed hereinfor treating a disease or condition mediated by TRPC protein activitywherein the patient has previously (e.g. within 24 hours) been treatedwith another therapeutic agent. The invention also provides the use ofanother therapeutic agent for treating a disease or condition mediatedby TRPC protein activity wherein the patient has previously (e.g. within24 hours) been treated with a compound as disclosed herein.

The pharmaceutical compositions can be administered alone or incombination with other molecules known to have a beneficial effect intreatment of kidney disease or more particularly in the treatment ofFSGS, nephrotic syndrome, minimal change diseases or diabetic kidneydisease. A combination therapy regimen may be additive, or it mayproduce synergistic results (e.g., improvement in kidney function whichis more than expected for the combined use of the two agents). In someembodiments, the present invention provide a combination therapy forpreventing and/or treating kidney disease or more particularly FSGS,nephrotic syndrome or minimal change diseases with a compound of theinvention and a second therapeutic agent selected from the groupconsisting of ACE/ARB (such as captopril, lisinopril or losartan),steroid therapy (such as prednisone), immunomodulators (such asmycophenolate mofetil, tacrolimus or cyclosporine A),adrenocorticotropic hormone analogs (such acthar gel), anti-CD20antibodies (such as rituximab), calcium channel blockers (such asamlodipine), diuretics (such as hydrochlorothiazide), antiplateletagents (such as dipyridamole), anticoagulants (such as heparin), DPP-4inhibitors (such as sitagliptin), SGLT2 inhibitors (such asdapagliflozin), anti-hyperlipidemia (such as rosuvastatin), anemiatherapy (darbepoetin alfa), or anti-hyperuricemia (febxostat).

In one embodiment, the invention provides a method of inhibiting theactivity of a TRPC protein, or more preferably inhibiting the activityof TRPC6 protein, in a subject, wherein the method comprisesadministering to the subject a therapeutically effective amount of thecompound according to the definition of Formula (I). The inventionfurther provides methods of inhibiting the activity of a TRPC protein,or more preferably inhibiting the activity of TRPC6 protein in a subjectby administering a compound as disclosed herein, wherein the methodcomprises administering to the subject a therapeutically effectiveamount of the compound as disclosed herein.

In one embodiment, the invention provides a compound as disclosedherein, for use as a medicament.

In one embodiment, the invention provides the use of a compound asdisclosed herein for the treatment of a disorder or disease in a subjectcharacterized by the activity of a TRPC protein, or more preferably theactivity of TRPC6 protein. In particular, the invention provides the useof a compound as disclosed herein for the treatment of a disorder ordisease mediated by the activity of a TRPC protein, or more preferablythe activity of TRPC6 protein, e.g., nephrotic syndrome, minimal changedisease, focal segmental glomerulosclerosis, collapsing glomerulopathy,membranous nephropathy, membranoproliferative glomerulonephritis, IGAnephropathy, acute renal failure, chronic renal failure, diabeticnephropathy, sepsis, pulmonary hypertension, acute lung disorder, acuterespiratory distress syndrome (ARDS), zheart failure, stroke, malignanttumor, or muscular dystrophy. In certain preferred aspects, theinvention provides for the use of a compound as disclosed herein for thetreatment of a disorder or disease mediated by the activity of TRPC6protein selected from nephrotic syndrome, membranous nephropathy andacute renal failure.

In one embodiment, the invention provides the use of a compound asdisclosed herein in the manufacture of a medicament for the treatment ofa disorder or disease in a subject characterized by activity of a TRPCprotein, or more preferably the activity of TRPC6 protein. Moreparticularly in the manufacture of a medicament for the treatment of adisease or disorder in a subject characterized by activity of a TRPCprotein, or more preferably the activity of TRPC6 protein, e.g.,nephrotic syndrome, minimal change disease, focal segmentalglomerulosclerosis, collapsing glomerulopathy, membranous nephropathy,membranoproliferative glomerulonephritis. IGA nephropathy, acute renalfailure, chronic renal failure, diabetic nephropathy, sepsis, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS), heart failure, stroke, malignant tumor, or muscular dystrophy.In certain preferred aspects, the invention provides the use of acompound as disclosed herein in the manufacture of a medicament for thetreatment of nephrotic syndrome, membranous nephropathy and acute renalfailure.

In one embodiment, the invention provides the use of a compound asdisclosed herein for the treatment of a disorder or disease in a subjectcharacterized by activity of a TRPC protein, or more preferably theactivity of TRPC6 protein. More particularly, the invention providesuses of the compounds provided herein in the treatment of a disease ordisorder characterized by activity of a TRPC protein, or more preferablythe activity of TRPC6 protein, e.g., nephrotic syndrome, minimal changedisease, focal segmental glomerulosclerosis, collapsing glomerulopathy,membranous nephropathy, membranoproliferative glomerulonephritis, IGAnephropathy, acute renal failure, chronic renal failure, diabeticnephropathy, sepsis, pulmonary hypertension, acute lung disorder, acuterespiratory distress syndrome (ARDS), heart failure, stroke, malignanttumor, or muscular dystrophy. In certain embodiments, the uses of thecompounds provided herein is for the treatment of a disease or disorderis selected from nephrotic syndrome, membranous nephropathy and acuterenal failure.

In a specific embodiment, the present invention provides use of thecompounds of the invention for treating or preventing nephroticsyndrome, membranous nephropathy, acute renal failure, sepsis, chronicrenal failure, diabetic nephropathy, pulmonary hypertension, acute lungdisorder, acute respiratory distress syndrome (ARDS), heart failure,stroke, malignant tumor or muscular dystrophy. In certain embodiments,patients who are currently asymptomatic but are at risk of developing asymptomatic nephrotic syndrome, membranous nephropathy, acute renalfailure, sepsis, chronic renal failure, diabetic nephropathy, pulmonaryhypertension, acute lung disorder, acute respiratory distress syndrome(ARDS), heart failure, stroke, malignant tumor or muscular dystrophy aresuitable for administration with a compound of the invention. The use intreating or preventing nephrotic syndrome, membranous nephropathy, acuterenal failure, sepsis, chronic renal failure, diabetic nephropathy,pulmonary hypertension, acute lung disorder, acute respiratory distresssyndrome (ARDS), heart failure, stroke, malignant tumor or musculardystrophyinclude, but are not limited to, uses in treating or preventingone or more symptoms or aspects of nephrotic syndrome, membranousnephropathy, acute renal failure, sepsis, chronic renal failure,diabetic nephropathy, pulmonary hypertension, acute lung disorder, acuterespiratory distress syndrome (ARDS), heart failure, stroke, malignanttumor or muscular dystrophy.

The invention further includes any variant of the present processes, inwhich an intermediate product obtainable at any stage thereof is used asstarting material and the remaining steps are carried out, or in whichthe starting materials are formed in situ under the reaction conditions,or in which the reaction components are used in the form of their saltsor optically pure materials.

The following examples are intended to illustrate the invention and arenot to be construed as being limitations thereon. Temperatures are givenin degrees centigrade (° C.). If not mentioned otherwise, allevaporations are performed under reduced pressure, typically betweenabout 15 mm Hg and 100 mm Hg (=20-133 mbar). The structure of finalproducts, intermediates and starting materials is confirmed by standardanalytical methods, e.g., microanalysis and spectroscopiccharacteristics, e.g., MS, IR, NMR. Abbreviations used are thoseconventional in the art.

The invention relates also to those forms of the process in which acompound obtainable as an intermediate at any stage of the process isused as starting material and the remaining process steps are carriedout, or in which a starting material is formed under the reactionconditions or is used in the form of a derivative, for example in aprotected form or in the form of a salt, or a compound obtainable by theprocess according to the invention is produced under the processconditions and processed further in situ.

All starting materials, building blocks, reagents, acids, bases,dehydrating agents, solvents and catalysts utilized to synthesize thecompounds of the present invention are either commercially available orcan be produced by organic synthesis methods known to one of ordinaryskill in the art.

EXPERIMENTAL

Unless otherwise noted, all materials were obtained from commercialsuppliers and used without further purification. All parts are by weightand temperatures are in degrees centigrade unless otherwise indicated.All microwave assisted reactions were conducted with a Smith Synthesizerfrom Biotage. Mass spectral data was determined by electrosprayionization technique. All examples were purified to >95% purity asdetermined by high-performance liquid chromatography. Unless otherwisestated, reactions were run at room temperature.

Commercially available materials were purchased from Sigma Aldrich, HDHPharma, Pharmablock, Alfa Aesar, Enovation Chemicals, and Combi-Blocks.

Compound names. i.e., IUPAC names, for compounds described in theinstant application were generated using ChemDraw compound namingsoftware.

The following abbreviations are used:

-   CDI—1,1′-carbonyldiimidazole-   DCM—dichloromethane-   DMSO—dimethyl sulfoxide-   DMF—N,N-dimethylformamide-   THF—tetrahydrofuran-   Et₂O—diethyl ether-   EtOAc—ethyl acetate-   EtOH—ethyl alcohol-   Ms—mes late-   MeCN—acetonitrile-   MeOH—methyl alcohol-   SFC—supercritical fluid chromatography-   TFA—trifluoroacetic acid-   tmp—2,2,6,6-tetramethylpiperidine-   h—hour-   min—min-   rt—room temperature (22-25° C.)-   mL milliliters-   μL microliters-   g grams-   μg micrograms-   mg milligrams-   μmoL micromolars

General Method of Preparation

The compounds described herein are prepared using techniques known toone skilled in the art through the reaction sequences depicted inschemes 1-6 as well as by other methods. Furthermore, in the followingschemes, where specific acids, bases, reagents, coupling agents,solvents, etc. are mentioned, it is understood that other suitableacids, bases, reagents, coupling agents, solvents, etc. may be used andare included within the scope of the present invention.

Synthesis of selected compounds of the present invention were preparedas described in Scheme 1. CDI coupling of the desired bis-anlineprovided the corresponding benzimidazolone. Subjection to refluxingPOCl₃ delivered the chlorobenzimidazole. These intermediates could bealkylated with a variety of electrophiles, then subjected to SnArconditions to provide the Boc protected penultimate intermediates.Exposure to a variety of acids effected Boc deprotection to furnish thefinal products.

An alternative approach to benzimidazole intermediates which was used tosynthesize additional compounds in the present invention is shown inScheme 2. CDI coupling of the desired bis-anline provided thecorresponding benzimidazolone. Subjection to refluxing POCl₃ deliveredthe chlorobenzimidazole. These intermediates were heated with base andnucleophile to provide the SnAr products. Alkyation with a variety ofelectrophiles followed by acidic Boc deprotection furnished the finalcompounds.

Additionally, examples in this invention could be synthesized by themethods shown in Scheme 3-6.

Isothiocyanate formation was accomplished using a variety of reagents.Addition of secondary amines followed by condensation with primaryamines provided the corresponding substituted quanidine. Intramoleculecyclizations were accomplished using copper catalysis. Final acidic Bocdeprotection furnished the desired compounds.

Subjection of substituted piperidines to cyanogen bromide provided thecorresponding piperidine-1-carbonitriles. These were susceptible tonucleophile attack by a variety of anliline nucleophiles, which werethen trapped with benzyl electrophiles. The corresponding guanidineunderwent intramolecule crosscoupling under palladium and coppercatalysis. Final Boc deprotection under acidic conditions furnished thedesired compounds.

Benzimidazoles were alkylated with a variety of electrophiles and base.These intermediates were subjected to Zn(tmp)₂, copper catalysis, andbenzoylhydroxylamines to furnish the aminated products. Final subjectionto acidic Boc deprotection conditions yielded the desired products.

SnAr transformations were accomplished on substitutedfluoro-nitrobenzenes using primary benzyl amines and base. Thecorresponding nitro intermediates were reduced with iron or zinc, thensubjected to CDI couplings and POCl₃ chlorination reactions. Theseintermediates were resubjected to SnAr conditions then Boc deprotectedunder acidic conditions to furnish the final compounds.

Intermediate 1:6-((2-chloro-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrileand Intermediate 2:6-((2-chloro-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

Step 1. 4,6-difluoro-1H-benzo[d]imidazol-2(3H)-one

3,5-difluorobenzene-1,2-diamine (210.0 g, 1.457 mol, 1.0 equiv) and CDI(236.0 g. 1.457 mol, 1.0 equiv) were dissolved in anhydrous THF (2.5 L.11.9 mL/g) and stirred for 12 h at room temperature. LCMS indicatedcompletion of the reaction. Reaction mixture was diluted with water (6.0L) and extracted with ethyl acetate (2×6.0 L). The combined organiclayer was dried over sodium sulphate, filtered and concentrated underreduced pressure to provide crude4,6-difluoro-1H-benzo[d]imidazol-2(3H)-one as black solid which was usedfor next step without further purification. ¹H NMR (400 MHz. DMSO-d₆): δ11.20 (s, 1H), 11.05 (s, 1H), 6.85 (td, J=10.7, 2.2 Hz, 1H), 6.69 (dd,J=8.6, 2.2 Hz, 1H). MS (ESI, pos. ion) m/z: 171.0 [M+1]

Step 2. 2-chloro-4,6-difluoro-1H-benzo[d]imidazole

4,6-difluoro-1H-benzo[d]imidazol-2(3H)-one (180.0 g, 1.058 mol, 1.0equiv) was suspended in POCl₃(2.0 L) and heated under stirring at 110°C. for 2 h. at which time LCMS indicated completion of the reaction.Excess POCl₃ was removed via vacuum distillation and the remainingresidue was diluted with acetonitrile (1.0 L) and sat. aq. sodiumbicarbonate solution (1.0 L), then extracted with ethyl acetate (2×4.0L). The combined organic layer was dried over sodium sulfate, filteredand concentrated under reduced pressure to provide2-chloro-4,6-difluoro-1H-benzo[d]imidazole as brown solid which was usedfor next reaction without further purification. ¹H NMR (400 MHz,DMSO-d₆): 13.40 (bs, 1H). 7.31-7.03 (m, 2H). MS (ESI, pos. ion) m/z:189.0 [M+11].

Step 3. 6-(hydroxymethyl)nicotinonitrile

(5-bromopyridin-2-yl)methanol (75.0 g, 399.0 mmol, 1.0 equiv), zinccyamide (141.0 g, 1.197 mol, 3.0 equiv) andtetrakis(triphenylphosphine)palladium(0) (46.1 g, 39.9 mmol, 0.1 equiv)were dissolved in N,N-dimethylformamide (750.0 mL. 10.0 mL/g) anddegassed with nitrogen for 30 minutes. The reaction mixture was heatedat 110° C. for 2 h. LCMS indicated formation of the product. Aftercompletion of the reaction, the mixture was allowed to cool to roomtemperature, diluted with water (700 mL) and extracted with ethylacetate (3×700 mL). The combined organic layers were dried over sodiumsulfate, filtered and concentrated under reduced pressure. The crudematerial was adsorbed onto a plug of silica gel (230-400 mesh) andpurified through a Biotage Isolera-one pre-packed silica gel column,eluting with a gradient of 40% ethyl acetate in hexane to provide6-(hydroxymethyl)nicotinonitrile as white solid. ¹H NMR (400 MHz,DMSO-d₆) δ 8.93 (dt, J=1.8, 0.8 Hz, 1H), 8.32-8.28 (m, 1H), 7.66 (dt,J=8.3, 0.9 Hz, 1H), 5.68 (td. J=5.9, 0.8 Hz, 1H), 4.64 (d, J=5.8 Hz,2H). MS (ESI, pos. ion) m/z: 135.0 [M+I]

Step 4. 6-(chloromethyl)nicotinonitrile and (5-cyanopyridin-2-yl)methylmethanesulfonate

6-(hydroxy methyl)nicotinonitrile (25.0 g, 186.0 mmol, 1.0 equiv) wasdissolved in dichloromethane (360.0 mL, 14.4 mL/g) and cooled to 0° C.N,N-diisopropylethylamine (48.8 mL, 280.0 mmol, 1.5 equiv) was added,followed by dropwise addition of methanesulfonyl chloride (16.0 g, 205.0mmol, 1.1 equiv) over 15 minutes. The reaction mixture was allowed towarm to room temperature and stirred for 45 min. LCMS indicatedformation of the product. The reaction mixture was diluted with water(500 mL) and extracted with DCM (2×250 mL). The combined organic layerswere dried over sodium sulfate, filtered and concentrated under reducedpressure to get crude material which was adsorbed into a plug of silicagel (230-400 mesh) and purified by chromatography through a BiotageIsolera-one pre-packed silica gel column, eluting with a gradient of 15%ethyl acetate in hexane to afford 6-(chloromethyl)nicotinonitrile (VI)as yellowish solid. ¹H NMR (400 MHz. DMSO-d₆) δ 9.03 (dd, J=2.2, 1.0 Hz.1H), 8.38 (dd, J=8.1, 2.2 Hz, 1H), 7.77 (dd, J=8.1, 0.9 Hz, 1H), 4.88(s, 21f). Further elution of the column with a gradient of 50% ethylacetate in hexane provided 5-cyanopyridin-2-yl)methyl methanesulfonateas brown solid. ¹H NMR (400 MHz, DMSO-d₆) δ 9.06 (dt, J=2.1, 1.0 Hz,1H). 8.41 (dt, J=8.2, 1.7 Hz, 1H), 7.73 (dd, J=8.2, 1.0 Hz, 1H). 5.42(d, J=1.1 Hz, 2H). 3.34 (s, 3H). MS (ESI, pos. ion) m/z: 213.2 [M+1].Both compounds were competent electrophiles in the alkylation (step 5).

Step 5.6-((2-chloro-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrileand6-((2-chloro-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

2-chloro-4,6-difluoro-1H-benzo[d]imidazole (50.0 g, 265.0 mmol, 1.0equiv) and 6-(chloromethyl)nicotinonitrile (40.5 g. 265.0 mmol, 1.0equiv) was dissolved in acetonitrile (500.0 mL, 10.0 mL/g) at roomtemperature. Cesium carbonate (138.0 g, 427.0 mmol, 1.6 equiv) was addedand the mixture was stirred at room temperature for 12 h. The reactionmixture was diluted with water (200 mL) and extracted with ethyl acetate(2×200 mL). The combined organic layers were dried over sodium sulfate,filtered and concentrate under reduced pressure. The crude material wasadsorbed onto a plug of silica gel (60-120 mesh) and purified by columnchromatography, eluting with a gradient of 25% ethyl acetate in hexaneto provide6-((2-chloro-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrileand6-((2-chloro-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrileas a mixture of isomers (light yellow solid). In some instances, themixture of isomers was carried forward without separation and in othersthe isomers were separated at this stage.

Step 6. Separation of6-((2-chloro-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(Intermediate 1) and6-((2-chloro-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(Intermediate 2)

1.0 g sample was dissolved in 20 mL Methanol. Column Lux C4 (250×50 mm.5 μm). Mobile phase: 70:30 (A:B). A: Liquid CO2, B: Methanol, Flow Rate:120 mL/min, Wave length: 220 nm, Sample load: 100 mg/injection, Inletpressure: 200-210 bar. Cycle time: 3.5, Run time: 10. In total, (51.0 gmixture of isomers) was separated by SFC to get6-((2-chloro-5,7-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(Intermediate 1, peak 1) and6-((2-chloro-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(Intermediate 2, peak 2) as yellow solids. Peak 1: ¹H NMR (400 MHz,DMSO-d₆): δ 8.90 (d, J=2.0 Hz. 1H). 8.37 (dd, J=8.2, 2.1 Hz, 1H), 7.70(d, J=8.2 Hz, 1H), 7.42 (dd, J=9.0, 2.2 Hz. 1H). 7.22 (ddd, J=11.9,10.3, 2.2 Hz. 1H). 5.79 (s, 2H). MS (ESI, pos. ion) m/z: 304.0 [M+11].Peak 2: ¹H NMR (400 MHz. DMSO-d&): δ 8.91 (t, J=3.0 Hz, 1H), 8.37 (ddd,J=8.2, 4.4, 2.1 Hz, 1H), 7.67 (dd, J=8.4, 4.2 Hz, 1H), 7.49 (dt, J=8.7,3.0 Hz, 1H), 7.20 (tdd, J=10.7, 4.5, 2.1 Hz, 1H), 5.79 (d, J=3.8 Hz.2H). MS (ESI, pos. ion) m/z: 304.0 [M+1].

The following intermediates were synthesized using a sequence analogousto that used to synthesize Intermediates 1 and 2 and general Scheme 7above:

TABLE 1 Alkylated Intermediates Compound MS Separation Int # StructureName 1H NMR MH+ Conditions 1

6-((2-chloro- 5,7-difluoro- 1H-benzo[d] imidazol-1- yl)methyl)nicotinonitrile ¹H NMR (400 MHz, DMSO-d6): δ 8.90 (d, J = 2.0 Hz, 1H),8.37 (dd, J = 8.2, 2.1 Hz, 1H), 7.70 (d, J = 8.2 Hz, 1H), 7.42 (dd, J =9.0, 2.2 Hz, 1H), 7.22 (ddd, J = 11.9, 10.3, 2.2 Hz, 1H), 5.79 (s, 2H)304.0 Column Lux C4, 30% MeOH, peak 1 2

6-((2-Chloro- 4,6-difluoro- 1H-benzo[d] imidazol-1- yl)methyl)nicotinonitrile ¹H NMR (400 MHz, DMSO-d6): δ 8.91 (t, J = 3.0 Hz, 1H),8.37 (ddd, J = 8.2, 4,4, 2.1 Hz, 1H), 7.67 (dd, J = 8.4, 4.2 Hz, 1H),7.49 (dt, J = 8.7, 3.0 Hz, 1H), 7.20 (tdd, J = 10.7, 4.5, 2.1 Hz, 1H),5.79 (d, J = 3.8 Hz, 2H) 304.0 Column Lux C4, 30% MeOH, peak 2 3

6-((2,6- dichloro-1H- benzo[d] imidazol-1- yl)methyl) nicotinonitrile ¹HNMR (400 MHz, DMSO-d₆): δ 8.90 (dd, J = 2.1, 0.9 Hz, 1H), 8.36 (dd, J =8.2, 2.2 Hz, 1H 7.80 (d, J = 2.1 Hz, 1H), 7.68- 7.60 (m, 2H), 7.29 (dd,J = 8.6, 2.1 Hz, 1H), 5.79 (s, 2H) 303.0 YMC Amyose SA, Methanol THF(70:30) 40%; peak 1 4

6-((2,5- dichloro-1H- benzo[d] imidazol-1- yl)methyl) nicotinonitrile 1HNMR (400 MHz, DMSO-d6): δ 8.90 (d, J = 2.1 Hz, 1H), 8.35 (dd, J = 8.2,2.1 Hz, 1H), 7.74 (d, J = 2.0 Hz, 1H), 7.66-7.55 (m, 2H), 7.33 (dd, J =8.7, 2.1 Hz, 1H), 5.79 (s, 2H) 303.0 YMC Amyose SA, Methanol THF (70:30)40%; peak 2 5

6-((2-chloro-6- fluoro-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile 1H NMR (400 MHz, DMSO-d6): δ 8.93-8.86 (m, 1H), 8.34(dd, J = 8.2, 2.1 Hz, 1H), 7.67-7.58 (m, 2H), 7.54 (dd, J = 9.2, 2.6 Hz,1H), 7.17-7.06 (m, 1H), 5.75 (s, 2H) 287.0 YMC Amyose SA, Methanol THF(70:30) 40%; peak 1 6

6-((2-chloro-5- fluoro-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile 1H NMR (400 MHz, DMSO-d6): δ 8.90 (d, J = 2.3 Hz, 1H),8.34 (dt, J = 8.0, 2.3 Hz, 1H), 7.59 (tq, J = 7.5, 2.2 Hz, 2H), 7.48(dq, J = 9.5, 2.4 Hz, 1H), 7.24-7.05 (m, 1H), 5.77 (s, 2H) 287.0 YMCAmyose SA, Methanol THF (70:30) 40%; peak 2 7

6-((2-chloro- 1H-benzo[d] imidazol-1- yl)methyl) nicotinonitrile 1H NMR(400 MHz, DMSO-d6): δ 8.92 (d, J = 2.1 Hz, 1H), 8.34 (dd, J = 8.1, 2.1Hz, 1H), 7.67- 7.54 (m, 3H), 7.30-7.245 (m, 2H), 5.76 (s, 2H) 269.2 — 8

6-((2-chloro-4- (trifluoromethyl)- 1H-benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 337.2 — 9^(a)

6-((2,6- dichloro-1H- imidazo[4,5- b]pyridin-1- yl)methyl)nicotinonitrile — 304.0 Separated at final product 10

2-chloro-1-((5- cyanopyridin- 2-yl)methyl)- 1H-benzo[d] imidazole-4-carbonitrile — 294.0 — 11

2-chloro-1-((5- cyanopyridin- 2-yl)methyl)-6- fluoro-1H- benzo[d]imidazole-4- carbonitrile — 312.2 — 12^(a)

6-((2-chloro-6- (trifluoromethoxy)- 1H-benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 353.2 Separated at final product 13^(a)

2-chloro-1-((5- chloropyridin- 2-yl)methyl)-6- (methylsulfonyl)-1H-benzo[d] imidazole — 357.8 Separated at final product 14

2-chloro-1-((5- chloropyrimidin- 2-yl)methyl)- 6-fluoro-1H- benzo[d]imidazole-4- carbonitrile — 323.8 — 15^(a)

2-chloro-4,6- difluoro-1-((5- fluoropyridin- 2-yl)methyl)- 1H-benzo[d]imidazole — 298.0 Separated at final product 16^(a)

2-chloro-4,6- difluoro-1-((5- fluoropyrimidin- 2-yl)methyl)- 1H-benzo[d]imidazole — 299.0 Separated at final product 17^(a)

2-chloro-1-((5- chloropyrimidin- 2-yl)methyl)- 6-fluoro-1H- benzo[d]imidazole — 297.0 Separated at final product 18

2-chloro-6- fluoro-1-((5- fluoropyrimidin- 2-yl)methyl)- 1H-benzo[d]imidazole-4- carbonitrile — 306.2 — 19^(a)

6-((2-chloro-6- (trifluoromethyl)- 1H-benzo [d]imidazol-1- yl)methyl)nicotinonitrile — 337.0 Separated at final product 20^(a)

6-((2,5- dichloro-6- methyl-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 317.0 Separated at final product 21^(a)

6-((2-chloro-6- (difluoromethoxy)- 1H-benzo [d]imidazol-1- yl)methyl)nicotinonitrile — 335.0 Separated at final product 22

6-((2-chloro-4- methoxy-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 299.2 Separated at final product 23

6-((2-chloro-4- methyl-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 283.2 — 24^(a)

6-((2-chloro-6- methoxy-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 299.2 Separated at final product 25^(a)

6-((2-chloro-6- fluoro-5- (trifluoromethyl)- 1H-benzo[d] imidazol-1-yl)methyl) nicotinonitrile — 355.0 Separated at final product 26^(a)

6-((2,6- dichloro-5- (trifluoromethyl)- 1H-benzo [d]imidazol-1-yl)methyl) nicotinonitrile — 371.0 Separated at final product 27^(a)

6-((2,6- dichloro-5- (trifluoromethoxy)- 1H-benzo [d]imidazol-1-yl)methyl) nicotinonitrile — 387.0 Separated at final product 28

6-((2,5,6- trichloro-1H- benzo[d] imidazol-1- yl)methyl) nicotinonitrile— 337.0 — 29

6-((2-chloro- 5,6-difluoro- 1H-benzo [d]imidazol- 1-yl)methyl)nicotinonitrile — 305.1 — 30

2-chloro-1-((5- chloropyridin- 2-yl)methyl)- 1H-benzo[d] imidazole —278.2 — 31^(a)

6-((2-chloro- 4,6-difluoro- 1H-benzo [d]imidazol-1- yl)methyl)nicotinonitrile — 305.2 Separated at final product 32

6-((2,4- dichloro-6- fluoro-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 321.0 — 33^(a)

2-chloro-1-((5- cyanopyridin- 2-yl)methyl)- 1H-benzo [d]imidazole-6-carbonitrile — 294.0 Separated at final product 34^(a)

6-((2-chloro-6- fluoro-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 287.0 Separated at final product 35

6-((2-chloro- 5,6-dimethyl- 1H-benzo [d]imidazol-1- yl)methyl)nicotinonitrile — 297.0 — 36

6-((2,4,6- trichloro-1H- benzo[d] imidazol-1- yl)methyl) nicotinonitrile— 336.8 — 37^(a)

6-((2,6- dichloro-1H- benzo[d] imidazol-1- yl)methyl) nicotinonitrile —304.0 Separated at final product 38

6-((2,4- dichloro-1H- benzo[d] imidazol-1- yl)methyl) nicotinonitrile —304.2 — 39^(a)

2-chloro-1-((5- cyanopyridin- 2-yl)methyl)- 1H-benzo [d]imidazole-6-carbonitrile — 294.2 Separated at final product 40^(a)

6-((2-chloro-6- methyl-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 283.2 Separated at final product 41^(a)

6-((2-chloro-5- fluoro-6- methyl-1H- benzo[d] imidazol-1- yl)methyl)nicotinonitrile — 301.2 Separated at final product 42^(a)

5-((2-chloro-6- (trifluoromethyl)- 1H-benzo[d] imidazol-1- yl)methyl)pyrazine-2- carbonitrile — 338.2 Separated at final product 43

5-((2-chloro- 5,6-difluoro- 1H-benzo [d]imidazol-1- yl)methyl)pyrazine-2- carbonitrile — 306.2 — 44^(a)

4-((2-chloro- 1H-benzo [d]imidazol-1- yl)methyl) benzonitrile — 268.2 —45^(a)

4-((2-chloro- 4,6-difluoro- 1H-benzo [d]imidazol-1- yl)methyl)benzonitrile — 304.2 Separated at final product 46^(a)

2-chloro-1-(4- cyanobenzyl)- 1H- benzo[d] imidazole-6- carbonitrile —293.2 Separated at final product 47^(a)

2-((2-chloro-6- fluoro-1H- benzo[d] imidazol-1- yl)methyl) pyrimidine-5-carbonitrile — 288.2 Separated at final product 48^(a)

2-chloro-6- fluoro-1-((5- methoxypyrimidin- 2-yl)methyl)-1H- benzo[d]imidazole — 293.2 Separated at final product 49^(a)

2-(2-chloro-6- fluoro-1H- benzo[d] imidazol-1-yl)- N-methyl-N- (2,2,2-trifluoroethyl) acetamide — 324.2 Separated at final product 50^(a)

2-(2-chloro-6- methoxy-1H- benzo[d] imidazol-1-yl)- N-methyl-N- (2,2,2-trifluoroethyl) acetamide — 336.0 Separated at final product 51^(a)

2-(2-chloro-6- methoxy-1H- benzo[d] imidazol-1- yl)-N,N-dimethylacetamide — 268.2 Separated at final product 52

2-(2-chloro-4- cyano-6-fluoro- 1H-benzo [d]imidazol- 1-yl)-N- methyl-N-(2,2,2- trifluoroethyl) acetamide — 349.2 — 53^(a)

2-(2-chloro-6- fluoro-4- methoxy-1H- benzo[d] imidazol-1-yl)-N-methyl-N- (2,2,2- trifluoroethyl) acetamide — 354.2 Separated at finalproduct 54^(a)

6-((2-chloro-5- (trifluoromethyl)- 3H- imidazo[4,5- b]pyridin-3-yl)methyl) nicotinonitrile — 338.2 Separated at final product 55^(a)

1-(azetidin-1- yl)-2-(6- bromo-2- chloro-1H- benzo[d] imidazol-1-yl)ethanone — 329.2 Separated at final product 56^(a)

2-(2-chloro-6- (trifluoromethyl)- 1H-benzo [d]imidazol- 1-yl)-1-morpholinoethanone — 348.2 Separated at final product 57^(a)

2-(2,6- dichloro-1H- benzo[d] imidazol-1-yl)-N,N- dimethylacetamide —273.0 Separated at final product 58^(a)

2-(2-chloro-6- (trifluoromethoxy)- 1H-benzo[d] imidazol-1-yl)-N,N-dimethylacetamide — 322.2 Separated at final product 59^(a)

2-(2-chloro-6- (trifluoromethoxy)- 1H-benzo[d] imidazol-1-yl)-1-morpholinoethanone — 264.2 Separated at final product ^(a)Mixture ofisomers formed through non-selective benzylation that were separated atfinal product or penultimate intermediate

Example 38:6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

Step 1, tert-butyl((3R,4R)-1-(1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate

1,1′-dimethyltriethylamine (1.300 ml, 7.44 mmol), tert-butyl((3R,4R)-4-fluoropiperidin-3-yl)carbamate (0.975 g, 4.47 mmol),6-((2-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(Intermediate 7, 1 g, 3.72 mmol), and dimethyl sulfoxide (7.44 ml) werecombined in a flask and heated to 130° C. for 36 hours. The mixture wascooled, poured into water, then extracted with EtOAc (3×). The organicswere combined, dried over Na2SO4, filtered, and concentrated. The crudematerial was loaded onto an 80 g RediSep ISCO cartridge, eluting with10-50% EtOAc in heptanes to provide tert-butyl((3R,4R)-1-(1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamateas a light orange foam. MS (ESI, pos. ion) m/z: 451.2 [M+1]

Note: n-butanol is a competent substitute for DMSO. Difluorinatedpiperidines required heating to 150 C.

Boc Deprotection Procedure with TFA (Procedure B)

Step 2.6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(Example 43)

Tert-butyl((3R,4R)-1-(1-((5-cyanopyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(1.31 g. 2.91 mmol, 1 equiv) was dissolved in DCM (10 mL) and slowlydripped into a flask of cooled (0 C) TFA (˜10 mL). After 1 hour,deprotection was complete. The mixture was poured onto an SCX column(pre-wetted with MeOH), flushed with MeOH, then eluted with methanolicammonia. The methanolic ammonia was concentrated, and the light orangeoil redissolved in MeCN/water, frozen, and lyophilized to provide thetitle compound as a light yellow solid. ¹H NMR (500 MHz, MeOD) δ8.81-8.92 (m, 1H), 8.23 (dd, J=8.30, 2.08 Hz, 1H). 7.49-7.66 (m, 2H),7.17-7.39 (m, 3H), 5.64 (s, 2H), 4.69-4.86 (m, 1H). 3.92-4.06 (m, 1H),3.61-3.79 (m, 2H), 3.20-3.32 (m, 2H), 2.24-2.41 (m, 1H), 1.92-2.14 (m,1H). (ESI, pos. ion) m/z: 351.2 [M+1]

Example 45:6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrilehydrochloride

Step 1. (S)-tert-butyl(1-(1-((5-cyanopyridin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-3-yl)carbamate

To a suspension of6-((2-chloro-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(150 mg. 0.523 mmol) and hunig's base (137 μl, 0.785 mmol) in 1-butanol(2093 μl) was added (S)-tert-butyl piperidin-3-ylcarbamate (115 mg,0.576 mmol). The reaction was stirred at 130° C. overnight. After 24hours, the reaction mixture was concentrated and purified by columnchromatography, eluting with 20-100% ethyl acetate in heptane, toprovide the title compound as an off white solid. (ESI, pos. ion) m/z:451.2 [M+1]

Boc Deprotection with HCl (Procedure A)

(S)-6-((2-(3-aminopiperidin-1-yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrilehydrochloride (Example 51)

Step 2. (S)-tert-butyl(1-(1-((5-cyanopyridin-2-yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-3-yl)carbamate(77 mg) was dissolved in dioxane (2 mL), and 4 N HCl in dioxane (585 μL,2.340 mmol) was added. The reaction was stirred at ambient temperature.After 16 hours, LC/MS analysis showed the reaction was complete. Thereaction mixture was concentrated in vacuo to provide the title compoundas an off white solid. ¹H NMR (400 MHz, d₆-DMSO) δ 8.94 (s, 1H), 8.48(br s, 2H), 8.40 (dd, J=2.18, 8.19 Hz, 1H), 7.77 (d. J=8.19 Hz. 1H).7.40 (dd, J=2.85, 8.66 Hz, 2H), 7.14 (dt. J=2.38, 9.33 Hz. 1H).5.65-5.84 (m, 2H). 3.89 (br d, J=10.57 Hz, 1H), 3.28-3.52 (m, 3H), 3.18(br t, J=9.80 Hz, 1H), 1.94-2.02 (m, 1H), 1.81-1.93 (m, 1H), 1.47-1.72(m, 2H). (ESI, pos. ion) m/z: 351.0 [M+1].

Note: The HCl salt was sometimes converted to a free base form using anaqueous work up or using ion exchange chromatography. Isolation of saltor free base is specified in table.

The following compounds were made in a manner analogous to that outlinedabove:

Example 8:6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrilewas synthesized on a 1 mmol scale following a procedure analogous tosequence outlined above using the TFA Boc deprotection (procedure B). Itwas separated at the Boc intermediate: Chiralcel OD-H. 25% IPA, peak 1.¹H NMR (5(00) MHz. MeOD) δ 8.86 (d, J=1.30 Hz, 1H). 8.14-8.20 (m. 1H).7.47 (d, J=8.56 Hz. 1H), 7.44 (d, J=8.30 Hz, 1H), 7.23 (d, J=2.08 Hz,1H), 7.19 (dd, J=1.95, 8.43 Hz, 1H), 5.53 (s, 2H), 4.33-4.50 (m, 1H),3.53-3.61 (m, 1H), 3.43-3.50 (m, 1H), 3.02-3.20 (m, 2H), 2.95 (dd,J=8.69, 12.33 Hz. 1H). 2.12-2.24 (m, 1H). 1.82-1.94 (m, 1H). (ESI, pos.ion) m/z: 387.2 [M+1].

Example 93:(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrilewas synthesized on a 1.9 mmol scale following a procedure analogous tothe sequence outlines above, using the TFA Boc deprotection (procedureB). It was separated at the chlorobenzimidazole intermediate (YMC AmyoseSA, Methanol THF (70:30) 40%; peak 1). ¹H NMR (500 MHz, MeOD) δ 8.84 (d,J=1.82 Hz, 1H), 8.15 (dd. J=2.08, 8.30 Hz, 1H). 7.40-7.52 (m, 2H).6.91-7.00 (m, 2H). 5.47-5.62 (m, 2H). 3.34-3.54 (m, 2H), 3.08-3.28 (m,3H), 2.21-2.36 (m, 1H), 2.00-2.21 (m, 1H). (ESI, pos. ion) m/z: 351.0[M+1].

The examples in Table 2 were synthesized using a sequence analogous tothat used to synthesize Examples 38, 45, 8, and 88 and general Scheme 8above:

TABLE 2 Compounds made following Scheme 8 Boc Deprotection procedure: A= HCl procedure, B = TFA procedure Boc Alkyl- Depro- ated tection Ex.Inter- Pro- MS # mediate Amine cedure Structure Compound Name MH+ 1 37

B

(S)-6-((2-(3- aminopiperidin-1-yl)-6- chloro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 367.0 2 37

B

(S)-6-((2-(3- aminopiperidin-1-yl)-5- chloro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 367.0 3 38

B

(S)-6-((2-(3- aminopiperidin-1-yl)-4- chloro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 367.0 4 38

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-4- chloro-1H-benzo[d]imidazol-1- yl)methylinicotinonitrile 385.0 5 38

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-4- chloro-1H-benzo[d]imidazol-1- yl)methylinicotinonitrile 385.0 6 37

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6- chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 385.0 7 37

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5- chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 385.0 8 37

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-6- chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 385.0 9 37

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-5- chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 385.0 10 38

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 4-chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 403.0 11 10

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-cyanopyridin-2-yl)methyl)-1H- benzo[d]imidazole-4- carbonitrile 376.0 12 37

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 403.0 13 37

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 5-chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 403.0 14 19

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile419.0 15 19

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile419.0 16 7

B

6-((2-((3S,4S)-3-amino- 4-fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile 351.2 17 7

B

(S)-6-((2-(5-amino-3,3- difluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile 369.2 18 11

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-cyanopyridin-2-yl)methyl)-6-fluoro-1H- benzo[d]imidazole-4- carbonitrile 394.4 19 12

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6-(trifluoromethoxy)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile435.4 20 12

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5-(trifluoromethoxy)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile435.4 21 25

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6- fluoro-5-(trifluoromethyl)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile437.0 22 25

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5- fluoro-6-(trifluoromethyl)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile437.0 23 7

B

6-((2-((3aS,7aR)- hexahydro-1H- pyrrolo[2,3-c]pyridin- 6(2H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 359.2 24 7

B

6-((2-((3aS,7aS)- hexahydro-1H- pyrrolo[2,3-c]pyridin- 6(2H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 359.2 25 7

B

6-((2-((3aS,7aS)- hexahydro-1H- pyrrolo[2,3-c]pyridin- 6(2H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 359.2 26 7

B

6-((2-((3aS,7aR)- hexahydro-1H- pyrrolo[2,3-c]pyridin- 6(2H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinointrile 359.2 27 7

B

(R)-6-((2-(1,6- diazaspiro[3.5]nonan-6- yl)-1H- benzo[d]imidazol-1-yl)methyl)nicotinointrile 359.2 28 7

B

(S)-6-((2-(1,6- diazaspiro[3.5]nonan-6- yl)-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 359.2 29 13

B

(3R,4R)-1-(1-((5- chloropyridin-2- yl)methyl)-6- (methylsulfonyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 438.0 30 13

B

(3R,4R)-1-(1-((5- chloropyridin-2- yl)methyl)-5- (methylsulfonyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 438.0 31 14

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H- benzo[d]imidazole-4- carbonitrile 404.0 32 15

B

(3R,4R)-1-(5,7- difluoro-1-((5- fluoropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 380.0 33 15

B

(3R,4R)-1-(4,6- difluoro-1-((5- fluoropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 380.0 34 16

B

(3R,4R)-1-(5,7- difluoro-1-((5- fluoropyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 381.2 35 16

B

(3R,4R)-1-(4,6- difluoro-1-((5- fluoropyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 381.2 36 18

B

2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-6- fluoro-1-((5-fluoropyrimidin-2- yl)methyl)-1H- benzo[d]imidazole-4- carbonitrile338.0 37 18

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6- fluoro-1-((5-fluoropyrimidin-2- yl)methyl)-1H- benzo[d]imidazole-4- carbonitrile338.0 38 7

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile 351.2 39 17

B

(3R,4S)-1-(1-((5- chloropyrimidin-2- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 379.2 40 17

B

(3R,4S)-1-(1-((5- chloropyrimidin-2- yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 379.2 41 39

B

(R)-2-(3-amino-4,4- difluoropiperidin-1-yl)- 1-((5-chloropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 404.2 42 39

B

(R)-2-(3-amino-4,4- difluoropiperidin-1-yl)- 1-((5-chloropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 404.2 43 28

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-dichloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 419.0 44 35

B

tert-butyl ((3R,4R)-1- (1-((5-cyanopyridin-2- yl)methyl)-5,6-dimethyl-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- yl)carbamate379.2 45 34

A

(S)-6-((2-(3- aminopiperidin-1-yl)-6- fluoro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile hydrochloride 351.0 46 34

A

(S)-6-((2-(3- aminopiperidin-1-yl)-5- fluoro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile hydrochloride 351.0 47 34

A

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-6- fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 369.0 48 34

A

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-5- fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 369.0 49 34

A

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5- fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 369.0 50 5

A

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5- fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 369.0 51 33

B

(S)-2-(3- aminopiperidin-1-yl)-1- ((5-cyanopyridin-2- yl)methyl)-1H-benzo[d]imidazole-6- carbonitrile 358.0 52 33

B

(S)-2-(3- aminopiperidin-1-yl)-1- ((5-cyanopyridin-2- yl)methyl)-1H-benzo[d]imidazole-5- carbonitrile 358.0 53 33

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-cyanopyridin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 376.0 54 33

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-cyanopyridin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 376.0 55 33

B

(R)-2-(3-amino-4,4- difluoropiperidin-1-yl)- 1-((5-cyanopyridin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 394.0 56 33

B

(R)-2-(3-amino-4,4- difluoropiperidin-1-yl)- 1-((5-cyanopyridin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 394.0 57 36

B

(S)-6-((2-(3- aminopiperidin-1-yl)- 4,6-dichloro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 401.0 58 36

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 4,6-dichloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 419.0 59 36

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)- 4,6-dichloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 419.0 60 36

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 4,6-dichloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 437.0 61 31

B

(S)-6-((2-(3- aminopiperidin-1-yl)- 4,6-difluoro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 369.0 62 31

B

(S)-6-((2-(3- aminopiperidin-yl)- 5,7-difluoro-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 369.0 63 31

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 4,6-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 387.0 64 31

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,7-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 387.0 65 31

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)- 4,6-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 387.0 66 31

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)- 5,7-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 387.0 67 31

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 5,7-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 405.0 68 33

B

2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-cyanopyridin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 376.0 69 33

B

2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-cyanopyridin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 376.0 70 7

A

(S)-6-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile 333.0 71 34

A

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 387.0 72 29

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 387.0 73 7

A

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile 351.0 74 7

A

6-((2-((1R,5S)-1- (aminomethyl)-3- azabicyclo[3.1.0]hexan- 3-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 345.2 75 7

A

6-((2-((1S,5R)-1- (aminomethyl)-3- azabicyclo[3.1.0]hexan- 3-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 345.2 76 7

A

6-((2-((3aR,4R,6aS)-4- aminohexahydrocyclopenta [c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 359.0 777

A

6-((2-((3aS,4S,6aR)-4- aminohexahydrocyclopenta [c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 359.0 787

A

6-((2-((3aR,4S,6aS)-4- aminohexahydrocyclopenta [c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 359.2 797

A

6-((2-((3aS,4R,6aR)-4- aminohexahydrocyclopenta [c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 359.2 807

A

(R)-6-((2-(3- (aminomethyl)pyrrolidin- 1-yl)-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile hydrochloride 333.2 81 7

A

(S)-6-((2-(3- (aminomethyl)pyrrolidin- 1-yl)-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile hydrochloride 333.2 82 28

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)- 5,6-dichloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 419.2 83 29

B

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 387.2 84 29

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 405.2 85 30

B

(R)-1-(1-((5- chloropyridin-2- yl)methyl)-1H- benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3- amine hydrochloride 378.2 86 30

B

(3R,4S)-1-(1-((5- chloropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 360.287 31

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 4,6-difluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 405.2 88 5

B

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 387.2 89 8

A

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 4-(trifluoromethyl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 437.2 90 8

A

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-4-(trifluoromethyl)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile419.2 91 8

A

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-4-(trifluoromethyl)-1H- benzo[d]imidazol-1- yl)methyl)nicotinonitrile419.2 92 9

A

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6-chloro-3H-imidazo[4,5- b]pyridin-3- yl)methyl)nicotinonitrile 386.2 93 9

A

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6-chloro-1H-imidazo[4,5- b]pyridin-1- yl)methyl)nicotinonitrile 386.0 94 9

A^(b)

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6-chloro-1H-imidazo[4,5- b]pyridin-1-yl)methyl)- N-(tert-butyl)nicotinamide 460.2 95 7

A

6-((2-((3R,4R)-3- amino-4- hydroxypiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 349.2 96 7

A

6-((2-((3S,4S)-3-amino- 4-hydroxypiperidin-1- yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 349.2 97 7

A

6-((2-(2,6- diazaspiro[3.4]octan-6- yl)-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 345.2 98 7

A

6-((2-((4aR,7aS)- hexahydropyrrolo[3,4- b][1,4]oxazin-6(2H)- yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 361.2 99 7

A

6-((2-((4aS,7aR)- hexahydropyrrolo[3,4- b][1,4]oxazin-6(2H)- yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 361.2 100 7

A

6-((2-((4aR,7aR)- hexahydropyrrolo[3,4- b][1,4]oxazin-6(2H)- yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 361.2 101 7

A

6-((2-((4aS,7aS)- hexahydropyrrolo[3,4- b][1,4]oxazin-6(2H)- yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 361.2 102 7

—

(S)-3-amino-1-(1-((5- cyanopyridin-2- yl)methyl)-1H- benzo[d]imidazol-2-yl)piperidine-3- carboxamide 376.2 103 7

—

(R)-3-amino-1-(1-((5- cyanopyridin-2- yl)methyl)-1H- benzo[d]imidazol-2-yl)piperidine-3- carboxamide 376.2 104 7

A

(S)-6-((2-(3-amino-3- (hydroxymethyl)piperidin- 1-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 363.2 105 7

A

(R)-6-((2-(3-amino-3- (hydroxymethyl)piperidin- 1-yl)-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 363.2 106 19

B

6-((2-((3R,4S)-3- amino-4-fluoro-1- piperidinyl)-6-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile419.2 107 19

B

6-((2-((3R,4S)-3- amino-4-fluoro-1- piperidinyl)-5-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile419.2 108 19

B

6-((2-((3R)-3-amino- 4,4-difluoro-1- piperidinyl)-6-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile437.2 109 19

B

6-((2-((3R)-3-amino- 4,4-difluoro-1- piperidinyl)-5-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile437.2 110 40

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5-methyl-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 365.2 111 40

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-6-methyl-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 365.2 112 20

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-6-chloro-5- methyl-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 399.1 113 20

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5-chloro-6- methyl-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 399.1 114 41

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-6-fluoro-5- methyl-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 383.1 115 41

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5-fluoro-6- methyl-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 383.1 116 7

B

6-((2-((3S)-3- (methylamino)-1- piperidinyl)-1H- benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile 347.2 117 7

B

6-((2-((3R)-3- (methylamino)-1- piperidinyl)-1H- benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile 347.2 118 21

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-6-(difluoromethoxy)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile417.2 119 21

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5-(difluoromethoxy)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile417.2 120 22

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-4-methoxy-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 381.2 121 23

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-4-methyl-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 365.2 122 a 42

B

5-((2-((3R,4S)-3- amino-4-fluoro-1- piperidinyl)-6-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-2- pyrazinecarboxamide438.2 123 a 42

B

5-((2-((3R,4S)-3- amino-4-fluoro-1- piperidinyl)-5-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-2- pyrazinecarboxamide438.2 124 27

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-6-chloro-5-(trifluoromethoxy)-1H- benzimidazol-1- yl)methyl)-3-pyridinecarbonitrile 469.2 125 27

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5-chloro-6-(trifluoromethoxy)-1H- benzimidazol-1- yl)methyl)-3-pyridinecarbonitrile 469.2 126 26

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-6-chloro-5-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile453.2 127 26

B

6-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5-chloro-6-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile453.2 128 7

B

6-((2-((5R)-1,7- diazaspiro[4.5-]decan-7- yl)-1H-benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile, 6- ((2-((5S)-1,7-diazaspiro[4.5]decan-7- yl)-1H-benzimidazol-1- yl)methyl)-3-pyridinecarbonitrile 373.2 129 7

B

6-((2-((6R)-1,8- diazaspiro[5.5]undecan- 8-yl)-1H-benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile 387.2 130 7

B

6-((2-((6S)-1,8- diazaspiro[5.5]undecan- 8-yl)-1H-benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile 387.2 131 7

B

6-((2-((4aR,8aR)- hexahydro-2H- pyrido[4,3- b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 375.2 132 7

B

6-((2-((4aS,8aS)- hexahydro-2H-pyrido[4,3- b][1,4]oxazin-6(5H)-yl)-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 375.2 133 a 43

B

5-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)-2- pyrazinecarboxamide 406.2 134 a 42

B

5-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-6-(trifluoromethyl)-1H- benzimidazol-1- yl)methyl)-2- pyrazinecarboxamide438.2 135 7

B

6-((2-((5R)-1,7- diazaspiro[4.5]decan-7- yl)-1H-benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile 373.2 136 7

B

6-((2-((5S)-1,7- diazaspiro[4.5]decan-7- yl)-1H-benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile 373.2 137 24

B

6-((2-((3R)-3-amino- 4,4-difluoro-1- piperidinyl)-5-methoxy-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 399.2 138 24

B

6-((2-((3R)-3-amino- 4,4-difluoro-1- piperidinyl)-6-methoxy-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 399.2 139 19

B

6-((2-((3S)-3- (methylamino)-1- piperidinyl)-6- (trifluoromethyl)-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 415.2 140 19

B

6-((2-((3S)-3- (methylamino)-1- piperidinyl)-5- (trifluoromethyl)-1H-benzimidazol-1- yl)methyl)-3- pyridinecarbonitrile 415.2 141 7

B

6-((2-((3S)-3-amino-3- methyl-1-piperidinyl)- 1H-benzimidazol-1-yl)methyl)-3- pyridinecarbonitrile 347.2 142 24

B

(S)-6-((2-(3- aminopiperidin-1-yl)-6- methoxy-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 2,2,2-trifluoroacetate 363.2 143 24

B

(S)-6-((2-(3- aminopiperidin-1-yl)-5- methoxy-1H- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 2,2,2-trifluoroacetate 363.2 144 32

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-4- chloro-6-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 2,2,2-trifluoroacetate403.0 145 24

A

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5- methoxy-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 381.0 146 24

A

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6- methoxy-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 381.0 147 24

A

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-6- methoxy-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 381.0 148 24

A

6-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-5- methoxy-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile hydrochloride 381.0 149 14

B

2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H- benzo[d]imidazole-4- carbonitrile 404.0 150 14

B

(R)-2-(3-amino-4,4- difluoropiperidin-1-yl)- 1-((5-chloropyrimidin-2-yl)methyl)-5-fluoro- 1H-benzo[d]imidazole- 7-carbonitrile 422.0 151 14

B

(R)-2-(3-amino-4,4- difluoropiperidin-1-yl)- 1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro- 1H-benzo[d]imidazole- 4-carbonitrile 422.0 152 3

B

6-((2-((3R,4R)-3- amino-4- hydroxypiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 383.2 153 3

B

6-((2-((3R,4S)-3- amino-4- hydroxypiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 383.2 154 44

B

(R)-4-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 368.2 155 44

A

4-((2-((3R,4R)-3- amino-4- hydroxypiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile compound with 4-((2-((3S,4S)-3-amino-4- hydroxypiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile (1:1) dihydrochloride 346.2

156 45

B

4-((2-(3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,7- difluoro-1H-benzimidazol-1- yl)methyl)benzonitrile 386.2 157 45

B

4-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-4,6- difluoro-1H-benzimidazol-1- yl)methyl)benzonitrile 386.2 158 46

B

2-((3R,4R)-3-amino-4- fluoro-1-piperidinyl)-1- (4-cyanobenzyl)-1H-benzimidazole-6- carbonitrile 375.2 159 46

B

2-((3R,4R)-3-amino-4- fluoro-1-piperidinyl)-1- (4-cyanobenzyl)-1H-benzimidazole-5- carbonitrile 375.2 160 46

B

2-((3R)-3-amino-4,4- difluoro-1-piperidinyl)- 1-(4-cyanobenzyl)-1H-benzimidazole-6- carbonitrile 393.3 161 46

B

2-((3R)-3-amino-4,4- difluoro-1-piperidinyl)- 1-(4-cyanobenzyl)-1H-benzimidazole-5- carbonitrile 393.3 162 44

A

(R)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 332.2 163 44

A

4-((2-((3R,4R)-3- amino-4- methylpiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 346.0 164 c 44

A

4-((2-(3-(aminomethyl)- 3-methylpyrrolidin-1- yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 346.2 165 44

A

4-((2-((3S,4R)-3- amino-4- phenylpyrrolidin-1-yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile & 4-((2-((3R,4S)-3amino-4- phenylpyrrolidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 394.2

166 44

A

(S)-4-((2-(3- aminopyrrolidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 318.2 167 44

A

(S)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 332.2 168 44

A

4-((2-(6-amino-2- azaspiro[4.4]nonan-2- yl)-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile 32.0 169 44

A

4-((2-(4- aminohexahydrocyclopenta [c]pyrrol-2(1H)-yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 358.2 170 44

A

4-((2-((3S,4S)-3-amino- 4-fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 350.2 171 44

A

4-((2-((3S,4R)-3- amino-4- fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 350.2 172 44

A

4-((2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 350.2 173 44

A

4-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 350.2 174 44

B

(R)-4-((2-(3- (aminomethyl)-3- fluoropyrrolidin-1-yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 2,2,2-trifluoroacetate350.0 175 44

B

(S)-4-((2-(3- (aminomethyl)-3- fluoropyrrolidin-1-yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 2,2,2-trifluoroacetate350.0 176 44

B

(R)-4-((2-(3- (aminomethyl)-3- hydroxypyrrolidin-1- yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 2,2,2-trifluoroacetate 348.2177 44

B

(S)-4-((2-(3- (aminomethyl)-3- hydroxypyrrolidin-1- yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 2,2,2-trifluoroacetate 348.2178 44

A

(S)-4-((2-(3- (aminomethyl)pyrrolidin- 1-yl)-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile Molecular Weight: 331.41 332.2 179 44

A

(R)-4-((2-(3- (aminomethyl)pyrrolidin- 1-yl)-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile Molecular Weight: 331.41 332.2 180 44

B

4-((2-((3S,4S)-3-amino- 4-methylpiperidin-1- yl)-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile 2,2,2-trifluoroacetate 346.2 181 44

B

4-((2-((3S,4R)-3- amino-4- methylpiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 2,2,2-trifluoroacetate 346.2 182 44

B

4-((2-((3R,4S)-3- amino-4- methylpiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 2,2,2-trifluoroacetate 346.2 183 44

A

4-((2-((1S,5R)-1- (aminomethyl)-3- azabicyclo[3.1.0]hexan- 3-yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 344.2 184 44

A

4-((2-((1R,5S)-1- (aminomethyl)-3- azabicyclo[3.1.0]hexan- 3-yl)-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 344.2 185 44

A

(R)-4-((2-(3- aminopiperidin-1-yl)-6- methoxy-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile 362.2 186 44

A

(R)-4-((2-(3- aminopiperidin-1-yl)-5- methoxy-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile 362.2 442 47

B

2-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6- fluoro-1H-benzo[d]imidazol-1- yl)methyl)pyrimidine-5- carbonitrile 370.2 443 47

B

2-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5- fluoro-1H-benzo[d]imidazol-1- yl)methyl)pyrimidine-5- carbonitrile 370.2 444 48

B

(3R,4R)-4-fluoro-1-(6- fluoro-1-((5- methoxypyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 375.4 445 49

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide406.2 446 48

B

(3R,4R)-4-fluoro-1-(5- fluoro-1-((5- methoxypyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 375.2 447 52

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 4-cyano-6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide431.2 448 51

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-methoxy-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 350.2 449 50

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-methoxy-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide418.0 450 51

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-methoxy-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 350.2 451 5

B

6-((2-((3R,4R)-3- amino-4- methoxypiperidin-1-yl)- benzo[d]imidazol-1-yl)methyl)nicotinonitrile 381.2 452 53

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6- fluoro-4-methoxy-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 399.2 453 54

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5-(trifluoromethyl)-3H- imidazo[4,5-b]pyridin-3- yl)methyl)nicotinonitrile420.2 454 17

B

(3R,4R)-1-(1-((5- chloropyrimidin-2- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)- 4-methoxypiperidin-3- amine 391.2 455 55

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-bromo-1H-benzo[d]imidazol-1-yl)- 1-(azetidin-1-yl)ethan- 1-one 412.0 456 17

B

(3R,4R)-1-(1-((5- chloropyrimidin-2- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)- 4-methoxypiperidin-3- amine 391.2 457 49

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide406.2 458 54

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5-(trifluoromethyl)-1H- imidazo[4,5-b]pyridin-1- yl)methyl)nicotinonitrile420.2 459 56

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- 1-morpholinoethan-1- one 430.2 460 49

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide406.2 461 57

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 354.2 462 49

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide406.2 463 17

B

6-((2-((3R,4S)-3- amino-4- methoxypiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 381.2 464 56

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- 1-morpholinoethan-1- one 430.2 465 49

B

(R)-2-(2-(3-amino-4,4- difluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide424.2 466 49

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide406.2 467 17

B

(3R,4S)-1-(1-((5- chloropyrimidin-2- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)- 4-methoxypiperidin-3- amine 391.2 468 58

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-(trifluoromethoxy)-1H-benzo[d]imidazol-1- yl)-N,N- dimethylacetamide 404.2 469 49

B

2-(6-fluoro-2-((3R,4R)- 4-fluoro-3- (methylamino)piperidin- 1-yl)-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide420.2 470 55

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-bromo-1H-benzo[d]imidazol-1-yl)- 1-(azetidin-1-yl)ethan- 1-one 410.0 471 57

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 5-chloro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 354.2 472 49

B

2-(6-fluoro-2-(1,7- diazaspiro[4.5]decan-7- yl)-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide428.2 473 56

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- 1-morpholinoethan-1- one 430.2 474 58

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-(trifluoromethoxy)-1H-benzo[d]imidazol-1- yl)-N,N- dimethylacetamide 404.2 475 59

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-(trifluoromethoxy)-1H-benzo[d]imidazol-1- yl)-1-morpholinoethan- 1-one 446.2 476 53

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-5- fluoro-7-methoxy-1H-benzo[d]imidazol-1- yl)methylinicotinonitrile 399.2 477 17

B

(3R,4S)-1-(1-((5- chloropyrimidin-2- yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)- 4-methoxypiperidin-3- amine 3912 478 56

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- 1-morpholinoethan-1- one 430.2 479 49

B

2-(5-fluoro-2-((3R,4R)- 4-fluoro-3- (methylamino)piperidin- 1-yl)-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide420.2 480 49

B

2-(2-(3-amino-4- methylpyrrolidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide388.2 481 49

B

2-(2-((3R,4R)-3-amino- 4-hydroxypiperidin-1- yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide404.2 482 49

B

(R)-2-(2-(3-amino-4,4- difluoropiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide424.2 483 49

B

2-(2-((3R,4R)-3-amino- 4-methoxypiperidin-1- yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide418.2 484 49

B

2-(2-((3R)-3-amino-4- hydroxypiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide404.2 485 49

B

2-(2-((3R,4R)-3-amino- 4-methoxypiperidin-1- yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide418.2 486 49

B

2-(2-(3-(aminomethyl)- 3-fluoropyrrolidin-1- yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide406.2 487 49

B

2-(2-(3-(aminomethyl)- 3-fluoropyrrolidin-1- yl)-5-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide406.2 488 49

B

2-(6-fluoro-2- ((4aR,8aR)-hexahydro- 2H-pyrido[4,3- b][1,4]oxazin-6(5H)-yl)-1H- benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2-trifluoroethyl)acetamide 430.2 489 49

B

(S)-2-(2-(3- aminopyrrolidin-1-yl)- 6-fluoro-1H- benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2- trifluoroethyl)acetamide 374.2 490 49

B

(R)-2-(2-(3- aminopyrrolidin-1-yl)- 6-fluoro-1H- benzo[d]imidazol-1-yl)-N-methyl-N-(2,2,2- trifluoroethyl)acetamide 374.2 491 49

B

(S)-2-(2-(3- (aminomethyl)pyrrolidin- 1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide388.2 492 49

B

2-(6-fluoro-2- ((4aR,8aR)-hexahydro- 2H-pyrido[4,3- b][1,4]oxazin-6(5H)-yl)-1H- benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2-trifluoroethyl)acetamide 430.2 493 49

B

2-(5-fluoro-2- ((4aS,8aS)-hexahydro- 2H-pyrido[4,3- b][1,4]oxazin-6(5H)-yl)-1H- benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2-trifluoroethyl)acetamide 430.2 a hydroysis of nitrite occurred duringSnAr b Ritter reactivity observed during Boc deprotection c unspecifiedsterochemistry designates mixtures of enantiomers or diastereomers

TABLE 3 Characterization data for compounds made following Scheme 8. Thecolumn “Separation Stage” indicates after which process stepregioisomers formed due to asymmetric benzimidazole substitution at R¹in Scheme 8 were separated during the preparation of the tabulated finalcompound (I = after preparation of the alkylated intermediate 1-59(where at least one R¹ is not hydrogen); B prior to boc deprotection; orF = final compound). SFC Isomer Ex. Freq., ¹HNMR Data SeparationSeparation #. Solvent (δ ppm) Stage Conditions 1 400 MHz 8.85 (dd, J =0.83, 2.07 Hz, 1H), 8.12-8.16 (m, 1H), B Chiralpak d₄- 7.44 (d, J = 8.50Hz, 1H), 7.37 (dd, J = 0.62, 8.29 Hz, AD-H, 20% MeOH 1H), 7.20 (d, J =1.66 Hz, 1H), 7.12-7.16 (m, 1H), MeOH, Peak 5.48 (s, 2H), 3.50 (br s,1H), 2.97-3.03 (m, 1H), 1 2.89-2.96 (m, 1H), 2.78-2.86 (m, 1H),1.92-2.01 (m, 1H), 1.81 (dt, J = 3.94, 8.71 Hz, 1H), 1.57-1.72 (m, 1H),1.31-1.42 (m, 1H) 2 500 MHz 8.81-8.86 (m, 1H), 8.11-8.17 (m, 1H),7.44-7.48 B Chiralpak d₄- (m, 1H), 7.36 (d, J = 8.04 Hz, 1H), 7.06-7.10(m, AD-H, 20% MeOH 2H), 5.49 (s, 2H), 3.52 (br dd, J = 1.69, 11.81 Hz,MeOH, Peak 1H), 2.97-3.06 (m, 1H), 2.90-2.96 (m, 1H), 2.80- 2 2.88 (m,1H), 1.92-2.01 (m, 1H), 1.82 (br dd, J = 4.28, 9.47 Hz, 1H), 1.58-1.71(m, 1H), 1.29-1.41 (m, 1H) 3 500 MHz 8.75-8.80 (m, 1H), 8.06 (d, J =8.30 Hz, 1H), 7.23- — — d₄- 7.31 (m, 1H), 7.11 (d, J = 7.27 Hz, 1H),6.94-7.05 MeOH (m, 2H), 5.44 (s, 2H), 3.48 (br d, J = 10.12 Hz, 1H),3.24-3.30 (m, 1H), 3.23-3.28 (m, 1H), 2.94-3.04 (m, 1H), 2.77-2.90 (m,2H), 1.83-1.96 (m, 1H), 1.71-1.81 (m, 1H), 1.51-1.65 (m, 1H), 1.19-1.35(m, 1H) 4 500 MHz 8.83 (s, 1H), 8.11-8.16 (m, 1H), 7.39 (d, J = 8.30 — —d₄- Hz, 1H), 7.18 (d, J = 7.01 Hz, 1H), 7.02-7.11 (m, MeOH 2H), 5.53 (s,2H), 4.33-4.52 (m, 1H), 3.59-3.66 (m, 1H), 3.50 (br d, J = 12.46 Hz,1H), 3.14-3.22 (m, 1H), 3.09 (dq, J = 4.02, 8.69 Hz, 1H), 2.95-3.05 (m,1H), 2.07-2.22 (m, 1H), 1.76-1.94 (m, 1H) 5 500 MHz 8.83 (s, 1H),8.10-8.15 (m, 1H), 7.37 (d, J = 8.04 — — d₄- Hz, 1H), 7.17 (d, J = 7.01Hz, 1H), 7.01-7.09 (m, MeOH 2H), 5.52 (s, 2H), 3.43 (dd, J = 4.15, 12.20Hz, 1H), 3.20-3.35 (m, 2H), 3.18-3.35 (m, 1H), 3.04-3.17 (m, 1H), 2.10(ddd, J = 4.93, 9.80, 14.34 Hz, 1H), 1.88-2.04 (m, 1H) 6 500 MHz 8.86(d, J = 1.30 Hz, 1H), 8.14-8.20 (m, 1H), 7.47 B Chiralcel OD- d₄- (d, J= 8.56 Hz, 1H), 7.44 (d, J = 8.30 Hz, 1H), 7.23 H, 25% IPA, MeOH (d, J =2.08 Hz, 1H), 7.19 (dd, J = 1.95, 8.43 Hz, peak 1 1H), 5.53 (s, 2H),4.33-4.50 (m, 1H), 3.53-3.61 (m, 1H), 3.43-3.50 (m, 1H), 3.02-3.20 (m,2H), 2.95 (dd, J = 8.69, 12.33 Hz, 1H), 2.12-2.24 (m, 1H), 1.82-1.94 (m,1H) 7 500 MHz 8.86 (d, J = 1.30 Hz, 1H), 8.13-8.20 (m, 1H), 7.49 BChiralcel OD- d₄- (s, 1H), 7.42 (d, J = 8.30 Hz, 1H), 7.12 (s, 2H), 5.54H, 25% IPA, MeOH (s, 2H), 4.43 (s, 1H), 3.57-3.63 (m, 1H), 3.45-3.55peak 2 (m, 1H), 3.12-3.20 (m, 1H), 3.03-3.12 (m, 1H), 2.97 (dd, J =8.82, 12.46 Hz, 1H), 2.12-2.24 (m, 1H), 1.80-1.96 (m, 1H) 8 500 MHz 8.86(d, J = 1.82 Hz, 1H), 8.14-8.19 (m, 1H), 7.47 B Chiralcel OD- d₄- (d, J= 8.56 Hz, 1H), 7.43 (d, J = 8.04 Hz, 1H), 7.22 H, 25% IPA, MeOH (s,1H), 7.13-7.20 (m, 1H), 5.53 (s, 2H), 4.75-4.81 peak 1 (m, 1H),3.37-3.43 (m, 1H), 3.01-3.29 (m, 4H), 2.08-2.20 (m, 1H), 1.88-2.03 (m,1H) 9 500 MHz 8.86 (d, J = 1.30 Hz, 1H), 8.14-8.19 (m, 1H), 7.49 BChiralcel OD- d₄- (s, 1H), 7.41 (d, J = 8.04 Hz, 1H), 7.12 (s, 2H), 5.53H, 25% IPA, MeOH (s, 2H), 3.37-3.49 (m, 2H), 3.28 (dd, J = 3.37, 8.04peak 2 Hz, 2H), 3.03-3.21 (m, 2H), 2.09-2.18 (m, 1H), 1.89-2.05 (m, 1H)10 500 MHz 8.84 (s, 1H), 8.16 (d, J = 8.04 Hz, 1H), 7.42-7.47 — — d₄-(m, 1H), 7.19-7.23 (m, 1H), 7.05-7.12 (m, 2H), MeOH 5.58 (s, 2H), 3.59(br d, J = 11.42 Hz, 1H), 3.45- 3.53 (m, 1H), 3.37 (ddd, J = 3.11, 9.54,12.78 Hz, 1H), 3.16-3.30 (m, 2H), 2.30 (tdd, J = 4.70, 9.67, 14.66 Hz,1H), 2.06-2.22 (m, 1H) 11 500 MHz 8.80-8.84 (m, 1H), 8.14-8.19 (m, 1H),7.45-7.51 — — d₄- (m, 2H), 7.41 (d, J = 8.04 Hz, 1H), 7.17 (t, J = 7.91MeOH Hz, 1H), 5.54-5.60 (m, 2H), 4.35-4.53 (m, 1H), 3.70-3.76 (m, 1H),3.50-3.64 (m, 1H), 3.19-3.26 (m, 1H), 3.14 (dq, J = 4.15, 8.82 Hz, 1H),2.98-3.08 (m, 1H), 2.11-2.23 (m, 1H), 1.80-1.95 (m, 1H) 12 500 MHz 8.85(d, J = 1.56 Hz, 1H), 8.15-8.20 (m, 1H), 7.48 F Chiralcel OD- d₄- (d, J= 8.56 Hz, 2H), 7.23 (d, J = 1.56 Hz, 1H), 7.19 H, 25% MeOH (dd, J =1.82, 8.56 Hz, 1H), 5.56 (s, 2H), 3.53 (br d, MeOH, peak J = 12.20 Hz,1H), 3.40-3.48 (m, 1H), 3.28-3.32 (m, 1 1H), 3.12-3.27 (m, 2H),2.23-2.37 (m, 1H), 2.06- 2.21 (m, 1H) 13 500 MHz 8.85 (d, J = 1.04 Hz,1H), 8.15-8.19 (m, 1H), 7.50 F Chiralcel OD- d₄- (s, 1H), 7.46 (d, J =8.04 Hz, 1H), 7.07-7.15 (m, H, 25% MeOH 2H), 5.54-5.59 (m, 2H), 3.56 (brd, J = 12.20 Hz, MeOH, peak 1H), 3.40-3.50 (m, 1H), 3.34-3.39 (m, 1H),3.13- 2 3.29 (m, 2H), 2.24-2.39 (m, 1H), 2.06-2.22 (m, 1H) 14 500 MHz8.85 (d, J = 1.82 Hz, 1H), 8.15-8.20 (m, 1H), 7.64 B Chiralcel OD- d₄-(d, J = 8.30 Hz, 1H), 7.44-7.54 (m, 3H), 5.59-5.64 H, 15% IPA, MeOH (m,2H), 4.36-4.54 (m, 1H), 3.60-3.71 (m, 1H), peak 1 3.48-3.56 (m, 1H),3.14-3.22 (m, 1H), 3.06-3.13 (m, 1H), 2.95-3.03 (m, 1H), 2.12-2.23 (m,1H), 1.81-1.97 (m, 1H) 15 500 MHz 8.82-8.87 (m, 1H), 8.15-8.21 (m, 1H),7.78 (s, B Chiralcel OD- d₄- 1H), 7.48 (d, J = 8.30 Hz, 1H), 7.41 (d, J= 8.56 Hz, H, 15% IPA, MeOH 1H), 7.31 (d, J = 8.30 Hz, 1H), 5.55-5.64(m, 2H), peak 2 4.35-4.54 (m, 1H), 3.60-3.69 (m, 1H), 3.50-3.59 (m, 1H),3.15-3.22 (m, 1H), 3.06-3.15 (m, 1H), 3.01 (dd, J = 8.82, 12.46 Hz, 1H),2.13-2.27 (m, 1H), 1.83-1.97 (m, 1H) 16 500 MHz 8.86 (d, J = 1.30 Hz,1H), 8.11-8.18 (m, 1H), 7.53 — — d₄- (d, J = 7.79 Hz, 1H), 7.37 (d, J =8.04 Hz, 1H), 7.18- MeOH 7.25 (m, 1H), 7.11-7.17 (m, 2H), 5.51-5.57 (m,2H), 4.37-4.53 (m, 1H), 3.57-3.65 (m, 1H), 3.40- 3.54 (m, 1H), 3.09-3.21(m, 2H), 2.99 (dd, J = 8.95, 12.33 Hz, 1H), 2.19 (Tt, J = 4.28. 13.62Hz, 1H), 1.81-1.98 (m, 1H) 17 500 MHz 8.90 (d, J = 1.30 Hz, 1H),8.08-8.16 (m, 1H), 7.33- — — d₄- 7.38 (m, 1H), 7.25 (d, J = 8.04 Hz,1H), 7.06-7.11 MeOH (m, 2H), 6.96-7.02 (m, 1H), 5.45 (s, 2H), 4.14- 4.23(m, 1H), 3.26 (br d, J = 13.23 Hz, 1H), 3.04- 3.16 (m, 1H), 2.83-2.94(m, 1H), 2.49-2.60 (m, 2H), 2.43-2.46 (m, 1H), 1.99-2.13 (m, 1H), 1.48-1.57 (m, 1H), 1.38 (qd, J = 7.28, 15.02 Hz, 1H) 18 500 MHz 8.83 (dd, J =1.56, 16.35 Hz, 1H), 8.18-8.25 (m, — — d₄- 1H), 7.50-7.61 (m, 1H),7.27-7.37 (m, 2H), 5.56 MeOH (d, J = 3.11 Hz, 2H), 3.04-3.26 (m, 3H),2.99 (br d, J = 8.04 Hz, 2H), 2.11-2.26 (m, 1H), 1.84-2.01 (m, 2H) 19500 MHz 8.84 (s, 1H), 8.13-8.21 (m, 1H), 7.52-7.58 (m, B Chiralpak d₄-1H), 7.43-7.50 (m, 1H), 7.06-7.18 (m, 2H), 5.50- AD-H, 15% MeOH 5.61 (m,2H), 4.39-4.58 (m, 1H), 3.64 (br d, MeOH, peak J = 12.46 Hz, 1H),3.45-3.56 (m, 1H), 3.11-3.22 (m, 1 2H), 3.01 (dd, J = 9.21, 12.33 Hz,1H), 2.12-2.25 (m, 1H), 1.83-1.97 (m, 1H) 20 500 MHz 8.85 (d, J = 1.30Hz, 1H), 8.11-8.21 (m, 1H), 7.45 B Chiralpak d₄- (d, J = 8.30 Hz, 1H),7.40 (s, 1H), 7.17-7.24 (m, AD-H, 15% MeOH 1H), 7.01-7.08 (m, 1H),5.51-5.60 (m, 2H), 4.37- MeOH, peak 4.54 (m, 1H), 3.61-3.68 (m, 1H),3.45-3.57 (m, 2 1H), 3.05-3.23 (m, 2H), 3.00 (dd, J = 9.08, 12.46 Hz,1H), 2.13-2.27 (m, 1H), 1.90 (ddd, J = 3.63, 9.60, 13.23 Hz, 1H) 21 500MHz 8.84 (d, J = 2.08 Hz, 1H), 8.16-8.22 (m, 1H), 7.46- B Phenomenex d₄-7.54 (m, 2H), 7.35 (d, J = 11.16 Hz, 1H), 5.57-5.61 Lux MeOH (m, 2H),4.36-4.53 (m, 1H), 3.64-3.72 (m, 1H), Cellulose-2, 3.49-3.59 (m, 1H),3.15-3.24 (m, 1H), 3.07-3.15 15% MeOH, (m, 1H), 3.02 (dd, J = 8.95,12.59 Hz, 1H), 2.18 (br peak 1 dd, J = 4.80, 9.21 Hz, 1H), 1.82-1.92 (m,1H) 22 500 MHz 8.83 (d, J = 1.30 Hz, 1H), 8.16-8.21 (m, 1H), 7.73 BPhenomenex d₄- (d, J = 6.23 Hz, 1H), 7.52 (d, J = 8.30 Hz, 1H), 7.21 LuxMeOH (d, J = 10.38 Hz, 1H), 5.58 (s, 2H), 4.34-4.53 (m, Cellulose-2,1H), 3.63 (br dd, J = 1.56, 12.46 Hz, 1H), 3.49 (br s, 15% MeOH, 1H),3.05-3.22 (m, 2H), 2.99 (dd, J = 8.82, 12.46 peak 2 Hz, 1H), 2.11-2.26(m, 1H), 1.89 (ddd, J = 3.63, 9.67, 13.43 Hz, 1H) 23 500 MHz 8.85 (s,1H), 8.06-8.13 (m, 1H), 7.51 (d, J = 7.79 B Chiralpak d₄- Hz, 1H), 7.29(d, J = 8.30 Hz, 1H), 7.05-7.22 (m, AD-H, 30% MeOH 3H), 5.49 (s, 2H),3.30-3.36 (m, 2H), 3.10-3.23 IPA, peak 1 (m, 3H), 2.94-3.09 (m, 1H),2.38 (qd, J = 6.47, 12.52 Hz, 1H), 1.88-2.03 (m, 2H), 1.66-1.88 (m, 2H)24 500 MHz 8.85 (s, 1H), 8.18-8.23 (m, 1H), 7.50-7.59 (m, B Chiralpakd₄- 2H), 7.27-7.33 (m, 1H), 7.21-7.26 (m, 2H), 5.61 AD-H, 30% MeOH (s,2H), 4.00 (br dd, J = 2.47, 12.85 Hz, 1H), 3.80- IPA, peak 2 3.91 (m,1H), 3.37-3.56 (m, 4H), 3.25 (br d, J = 2.34 Hz, 3H), 2.13-2.28 (m, 3H),1.88-2.07 (m, 3H), 1.69-1.83 (m, 1H) 25 500 MHz 8.85 (s, 1H), 8.06-8.13(m, 1H), 7.51 (d, J = 7.79 B Chiralpak d₄- Hz, 1H), 7.29 (d, J = 8.30Hz, 1H), 7.05-7.22 (m, AD-H, 30% MeOH 3H), 5.49 (s, 2H), 3.30-3.36 (m,2H), 3.10-3.23 IPA, peak 3 (m, 3H), 2.94-3.09 (m, 1H), 2.38 (qd, J =6.47, 12.52 Hz, 1H), 1.88-2.03 (m, 2H), 1.66-1.88 (m, 2H) 26 500 MHz8.85 (s, 1H), 8.18-8.23 (m, 1H), 7.50-7.59 (m, B Chiralpak d₄- 2H),7.27-7.33 (m, 1H), 7.21-7.26 (m, 2H), 5.61 AD-H, 30% MeOH (s, 2H), 4.00(br dd, J = 2.47, 12.85 Hz, 1H), 3.80- IPA, peak 4 3.91 (m, 1H),3.37-3.56 (m, 4H), 3.25 (br d, J = 2.34 Hz, 3H), 2.13-2.28 (m, 3H),1.88-2.07 (m, 3H), 1.69-1.83 (m, 1H) 27 400 MHz 8.83 (dd, J = 0.62, 2.07Hz, 1H), 8.08 (dd, J = 2.07, B Chiralpak IC, d₄- 8.09 Hz, 1H), 7.49-7.54(m, 1H), 7.32 (d, J = 8.29 40% MeOH, MeOH Hz, 1H), 7.07-7.19 (m, 3H),5.45-5.52 (m, 2H), peak 1 3.38-3.45 (m, 2H), 2.99-3.17 (m, 2H),1.94-2.14 (m, 2H), 1.57-1.86 (m, 4H) 28 400 MHz 8.83 (dd, J = 0.83, 2.07Hz, 1H), 8.06-8.11 (m, 1H), B Chiralpak IC, d₄- 7.49-7.55 (m, 1H), 7.32(d, J = 8.29 Hz, 1H), 7.05- 40% MeOH, MeOH 7.19 (m, 3H), 5.47-5.52 (m,2H), 3.37-3.46 (m, peak 2 2H), 3.01-3.18 (m, 2H), 1.96-2.18 (m, 2H),1.56- 1.84 (m, 4H) 29 500 MHz 8.49 (d, J = 2.34 Hz, 1H), 7.83-7.87 (m,1H), 7.75- B Chiralcel OD- d₄- 7.79 (m, 2H), 7.66 (d, J = 8.30 Hz, 1H),7.36 (d, H, 25% MeOH J = 8.56 Hz, 1H), 5.52 (s, 2H), 4.42-4.59 (m, 1H),MeOH, peak 3.77 (dtd, J = 1.69, 4.27, 12.62 Hz, 1H), 3.56-3.67 1 (m,1H), 3.18-3.26 (m, 2H), 3.09 (s, 3H), 3.02- 3.08 (m, 1H), 2.15-2.26 (m,1H), 1.84-1.96 (m, 1H) 30 500 MHz 8.48 (d, J = 2.34 Hz, 1H), 8.04-8.08(m, 1H), 7.83- B Chiralcel OD- d₄- 7.88 (m, 1H), 7.69 (dd, J = 1.82,8.56 Hz, 1H), 7.37 H, 25% MeOH (dd, J = 4.02, 8.43 Hz, 2H), 5.48-5.53(m, 2H), MeOH, peak 4.47-4.65 (m, 1H), 3.79 (dtd, J = 1.69, 4.27, 12.621 Hz, 1H), 3.58-3.67 (m, 1H), 3.33-3.38 (m, 1H), 3.17-3.25 (m, 1H),3.07-3.14 (m, 4H), 2.18-2.29 (m, 1H), 1.87-2.03 (m, 1H) 31 400 MHz8.77-8.82 (m, 2H), 7.35-7.43 (m, 1H), 7.28-7.32 — — d₄- (m, 1H), 5.54(s, 2H), 4.38-4.60 (m, 1H), 3.76 MeOH (dtd, J = 1.97, 4.31, 12.62 Hz,1H), 3.56-3.68 (m, 1H), 3.16-3.26 (m, 2H), 2.97-3.10 (m, 1H), 2.12- 2.26(m, 1H), 1.79-1.98 (m, 1H) 32 400 MHz 8.37 (d, J = 2.90 Hz, 1H),7.57-7.64 (m, 1H), 7.33 B Regis Whelk- d₄- (dd, J = 4.35, 8.71 Hz, 1H),7.05 (dd, J = 2.07, 8.91 O, 20% MeOH Hz, 1H), 6.73 (ddd, J = 2.18, 9.85,11.61 Hz, 1H), MeOH, peak 5.49 (s, 2H), 4.39-4.60 (m, 1H), 3.70 (dtd, J= 1.76, 2 4.28, 12.49 Hz, 1H), 3.49-3.61 (m, 1H), 3.11-3.31 (m, 2H),3.04 (dd, J = 9.12, 12.44 Hz, 1H), 2.13- 2.28 (m, 1H), 1.83-2.04 (m, 1H)33 400 MHz 8.41 (d, J = 2.90 Hz, 1H), 7.57-7.64 (m, 1H), 7.35 B RegisWhelk- d₄- (dd, J = 4.15, 8.71 Hz, 1H), 6.71-6.85 (m, 2H), 5.41 O, 20%MeOH (s, 2H), 4.32-4.54 (m, 1H), 3.61 (dtd, J = 1.66, 4.17, MeOH, peak12.39 Hz, 1H), 3.43-3.53 (m, 1H), 3.06-3.20 (m, 1 2H), 2.97 (dd, J =8.60, 12.34 Hz, 1H), 2.11-2.25 (m, 1H), 1.80-1.97 (m, 1H) 34 400 MHz8.66-8.74 (m, 2H), 6.86-6.92 (m, 1H), 6.72-6.82 B Regis Whelk- d₄- (m,1H), 5.51 (s, 2H), 4.36-4.59 (m, 1H), 3.64 O, 15% MeOH (dtd, J = 1.87,4.28, 12.39 Hz, 1H), 3.47-3.57 (m, MeOH, peak 1H), 3.09-3.22 (m, 2H),2.99 (dd, J = 8.91, 12.44 2 Hz, 1H), 2.07-2.26 (m, 1H), 1.75-1.99 (m,1H) 35 400 MHz 8.67-8.72 (m, 2H), 7.03-7.08 (m, 1H), 6.68-6.77 B RegisWhelk- d₄- (m, 1H), 5.62 (d, J = 0.83 Hz, 2H), 4.44-4.65 (m, O, 15% MeOH1H), 3.69 (dtd, J = 1.76, 4.35, 12.54 Hz, 1H), 3.44- MeOH, peak 3.58 (m,1H), 3.24-3.32 (m, 1H), 3.12-3.19 (m, 1 1H), 3.05 (dd, J = 9.43, 12.54Hz, 1H), 2.17-2.27 (m, 1H), 1.84-2.01 (m, 1H) 36 500 MHz 8.73 (s, 2H),7.39-7.44 (m, 1H), 7.35 (dd, J = 2.34, — — d₄- 9.34 Hz, 1H), 5.57 (d, J= 4.15 Hz, 2H), 5.00-5.16 MeOH (m, 1H), 3.72-3.85 (m, 2H), 3.46-3.54 (m,2H), 3.35-3.44 (m, 1H), 1.98-2.19 (m, 2H) 37 500 MHz 8.72 (s, 2H),7.37-7.41 (m, 1H), 7.31 (dd, J = 2.47, — — d₄- 9.47 Hz, 1H), 5.55 (s,2H), 4.41-4.60 (m, 1H), 3.78 MeOH (dtd, J = 1.82, 4.25, 12.78 Hz, 1H),3.56-3.70 (m, 1H), 3.16-3.29 (m, 2H), 3.07 (dd, J = 9.34, 12.72 Hz, 1H),2.14-2.24 (m, 1H), 1.83-1.96 (m, 1H) 38 500 MHz 8.81-8.92 (m, 1 H), 8.23(dd, J = 8.30, 2.08 Hz, 1 — — d₄- H), 7.49-7.66 (m, 2H), 7.17-7.39 (m,3H), 5.64 (s, MeOH 2H), 4.69-4.86 (m, 1H), 3.92-4.06 (m, 1H), 3.61- 3.79(m, 2H), 3.20-3.32 (m, 2H), 2.24-2.41 (m, 1H), 1.92-2.14 (m, 1H) 39 500MHz 8.74-8.81 (m, 2 H), 7.39-7.51 (m, 1 H), 7.00 B Chiralpak IC, d₄-(dd, J = 8.95, 2.47 Hz, 1 H), 6.94 (ddd, J = 9.86, 20% IPA, MeOH 8.82,2.60 Hz, 1 H), 5.51 (s, 2 H), 4.98 (dt, J = 5.26, peak 1 2.43 Hz, 1 H),3.48 (dd, J = 11.94, 3.89 Hz, 1 H), 3.19-3.41 (m, 5 H), 1.92-2.21 (m, 2H) 40 500 MHz 8.78 (s, 2 H), 7.04-7.25 (m, 2 H), 6.80-6.96 (m, BChiralpak IC, d₄- 1 H), 5.45-5.61 (m, 2 H), 3.42-3.58 (m, 1 H), 20% IPA,MeOH 3.17-3.40 (m, 5 H), 1.88-2.23 (m, 2 H) peak 2 41 500 MHz 8.81 (s,2H), 7.67-7.71 (m, 1H), 7.61 (d, J = 8.30 B Chiralpak OJ, d₄- Hz, 1H),7.49-7.53 (m, 1H), 5.61 (s, 2H), 3.69- 15% MeOH, MeOH 3.77 (m, 1H),3.58-3.66 (m, 1H), 3.43-3.53 (m, peak 2 1H), 3.36-3.43 (m, 1H),3.23-3.30 (m, 1H), 2.14- 2.41 (m, 2H) 42 500 MHz 8.79 (s, 2H), 7.80-7.86(m, 1H), 7.42-7.48 (m, B Chiralpak OJ, d₄- 1H), 7.37 (d, J = 8.30 Hz,1H), 5.61 (s, 2H), 3.66- 15% MeOH, MeOH 3.74 (m, 1H), 3.55-3.63 (m, 1H),3.34-3.53 (m, peak 1 3H), 3.22-3.30 (m, 1H), 2.29-2.41 (m, 1H), 2.07-2.27 (m, 1H) 43 400 MHz 8.93 (d, J = 1.35 Hz, 1H), 8.32 (dd, J = 2.18,8.19 — — d₆- Hz, 1H), 7.67 (s, 1H), 7.54 (s, 1H), 7.52-7.56 (m, DMSO1H), 7.49 (d, J = 7.92 Hz, 1H), 5.56 (s, 2H), 4.22- 4.48 (m, 1H),3.36-3.45 (m, 2H), 2.97-3.09 (m, 1H), 2.72-2.94 (m, 2H), 1.97-2.11 (m,1H), 1.61- 1.77 (m, 1H) 44 400 MHz 8.96 (s, 1H), 8.27 (dd, J = 2.18,8.19 Hz, 1H), 7.27 — — d₆- (d, J = 7.98 Hz, 1H), 7.23 (s, 1H), 6.92 (s,1H), 5.44 DMSO (s, 2H), 4.21-4.48 (m, 1H), 3.35 (br s, 3H), 2.86- 3.03(m, 2H), 2.74 (dd, J = 8.60, 12.44 Hz, 1H), 2.24 (s, 3H), 2.20 (s, 3H),1.93-2.12 (m, 1H), 1.87 (br s, 1H), 1.64-1.82 (m, 1H) 45 400 MHz8.92-8.95 (m, 1H), 8.36-8.50 (m, 3H), 7.76 (d, B Chiralcel OD- d₆- J =8.09 Hz, 1H), 7.53-7.60 (m, 1H), 7.35-7.43 (m, H, 15% IPA DMSO 1H), 7.18(t, J = 9.23 Hz, 1H), 5.65-5.84 (m, 2H), Peak 1 3.86 (br d, J = 10.47Hz, 1H), 3.26-3.52 (m, 3H), 3.15 (br t, J = 9.90 Hz, 1H), 1.82-2.01 (m,2H), 1.40-1.69 (m, 2H) 46 400 MHz 8.94 (s, 1H), 8.48 (br s, 2H), 8.40(dd, J = 2.18, 8.19 B Chiralcel OD- d₆- Hz, 1H), 7.77 (d, J = 8.19 Hz,1H), 7.40 (dd, H, 15% IPA DMSO J = 2.85, 8.66 Hz, 2H), 7.14 (dt, J =2.38, 9.33 Hz, Peak 2 1H), 5.65-5.84 (m, 2H), 3.89 (br d, J = 10.57 Hz,1H), 3.28-3.52 (m, 3H), 3.18 (br t, J = 9.80 Hz, 1H), 1.94-2.02 (m, 1H),1.81-1.93 (m, 1H), 1.47-1.72 (m, 2H) 47 400 MHz 8.93 (s, 1H), 8.71 (brs, 2H), 8.38 (dd, J = 1.75, 8.24 B Chiralcel OD- d₆- Hz, 1H), 7.73 (d, J= 8.17 Hz, 1H), 7.57 (dd, H, 15% IPA DMSO J = 4.54, 8.69 Hz, 1H), 7.36(br d, J = 8.30 Hz, 1H), Peak 1 7.16 (t, J = 8.68 Hz, 1H), 5.65-5.82 (m,2H), 5.06- 5.24 (m, 1H), 3.79 (br d, J = 12.07 Hz, 1H), 3.62- 3.74 (m,1H), 3.36-3.52 (m, 3H), 3.24-3.33 (m, 1H), 2.09-2.20 (m, 1H), 1.88-2.09(m, 1H) 48 400 MHz 8.94 (s, 1H), 8.66 (br s, 3H), 8.37 (dd, J = 1.82,8.17 B Chiralcel OD- d₆- Hz, 1H), 7.67 (d, J = 8.17 Hz, 1H), 7.37 (dd,H, 15% IPA DMSO J = 2.14, 9.02 Hz, 1H), 7.31 (br dd, J = 4.41, 8.69 Peak2 Hz, 1H), 7.07 (t, J = 8.71 Hz, 1H), 5.60-5.78 (m, 2H), 5.05-5.24 (m,1H), 3.62-3.78 (m, 2H), 3.36- 3.51 (m, 2H), 3.22-3.31 (m, 1H), 2.09-2.18(m, 1H), 1.93-2.07 (m, 1H) 49 400 MHz 8.90-8.96 (m, 1H), 8.87 (br s,2H), 8.40 (dd, B Chiralcel OD- d₆- J = 1.95, 8.17 Hz, 1H), 7.76 (d, J =8.30 Hz, 1H), H, 15% IPA DMSO 7.58 (dd, J = 4.54, 8.69 Hz, 1H), 7.39 (brd, J = 7.40 Peak 1 Hz, 1H), 7.18 (t, J = 8.78 Hz, 1H), 5.68-5.84 (m,2H), 4.86-5.05 (m, 1H), 4.04 (br d, J = 12.46 Hz, 1H), 3.59-3.73 (m,1H), 3.33-3.53 (m, 2H), 3.22 (br t, J = 11.42 Hz, 1H), 2.22-2.32 (m,1H), 1.75- 1.92 (m, 1H) 50 400 MHz 8.94 (s, 1H), 8.90 (br s, 2H), 8.39(dd, J = 1.62, 8.24 B Chiralcel OD- d₆- Hz, 1H), 7.76 (d, J = 8.17 Hz,1H), 7.35-7.45 (m, H, 15% IPA DMSO 2H), 7.13 (t, J = 8.77 Hz, 1H),5.68-5.84 (m, 2H), Peak 2 4.87-5.07 (m, 1H), 4.07 (br d, J = 12.72 Hz,1H), 3.60-3.73 (m, 1H), 3.36-3.53 (m, 2H), 3.25 (br t, J = 11.55 Hz,1H), 2.23-2.32 (m, 1H), 1.78-1.91 (m, 1H) 51 400 MHz 8.94 (d, J = 1.45Hz, 1H), 8.32 (dd, J = 2.18, 8.19 B Chiralpak d₆- Hz, 1H), 7.72 (d, J =0.93 Hz, 1H), 7.45-7.55 (m, AD-H, 20% DMSO 3H), 5.56 (s, 2H), 3.48 (brd, J = 11.71 Hz, 1H), methanol 3.34-3.42 (m, 1H), 2.84-2.95 (m, 1H),2.61-2.78 Peak 1 (m, 2H), 1.74-1.83 (m, 1H), 1.59-1.72 (m, 1H),1.40-1.58 (m, 1H), 1.03-1.29 (m, 1H) 52 400 MHz 8.93 (d, J = 1.35 Hz,1H), 8.32 (dd, J = 2.18, 8.19 B Chiralpak d₆- Hz, 1H), 7.89 (d, J = 1.14Hz, 1H), 7.47-7.54 (m, AD-H, 20% DMSO 1H), 7.42 (d, J = 1.45 Hz, 1H),7.32 (d, J = 8.29 Hz, methanol 1H), 5.57 (s, 2H), 3.38-3.50 (m, 1H),3.29-3.37 Peak 2 (m, 1H), 2.87 (br s, 1H), 2.78 (br s, 1H), 2.66 (br dd,J = 9.07, 11.87 Hz, 1H), 1.74-1.85 (m, 1H), 1.62-1.74 (m, 1H), 1.43-1.57(m, 1H), 1.11-1.31 (m, 1H) 53 400 MHz 8.93 (dd, J = 0.73, 2.07 Hz, 1H),8.33 (dd, J = 2.07, B Chiralpak d₆- 8.19 Hz, 1H), 7.74 (d, J = 0.93 Hz,1H), 7.48-7.58 AD-H, 25% DMSO (m, 3H), 5.61 (s, 2H), 4.25-4.48 (m, 1H),3.38- methanol 3.57 (m, 2H), 3.03-3.16 (m, 1H), 2.80-2.92 (m, Peak 12H), 1.97-2.13 (m, 1H), 1.61-1.80 (m, 3H) 54 400 MHz 8.92 (s, 1H), 8.33(dd, J = 2.12, 8.14 Hz, 1H), 7.91 B Chiralpak d₆- (d, J = 1.14 Hz, 1H),7.54 (d, J = 8.29 Hz, 1H), 7.45 AD-H, 25% DMSO (dd, J = 1.50, 8.24 Hz,1H), 7.33 (d, J = 8.29 Hz, methanol 1H), 5.61 (s, 2H), 4.25-4.48 (m,1H), 3.36-3.52 Peak 2 (m, 3H), 3.07 (br s, 1H), 2.79-2.95 (m, 2H), 1.96-2.18 (m, 1H), 1.65-1.80 (m, 2H) 55 400 MHz 8.88 (d, J = 1.35 Hz, 1H),8.00 (dd, J = 2.13, 8.14 B Chiralpak CDCl₃ Hz, 1H), 7.64 (d, J = 8.19Hz, 1H), 7.45-7.54 (m, AD-H, 20% 1H), 7.28 (d, J = 1.04 Hz, 1H),7.21-7.26 (m, 1H), IPA 5.36-5.47 (m, 2H), 3.43-3.63 (m, 3H), 3.14-3.33Peak 1 (m, 2H), 2.27-2.40 (m, 1H), 2.10-2.24 (m, 1H), 1.75 (br s, 2H) 56400 MHz 8.89 (d, J = 1.35 Hz, 1H), 7.99 (dd, J = 2.07, 8.09 B ChiralpakCDCl₃ Hz, 1H), 7.92 (d, J = 0.93 Hz, 1H), 7.42 (dd, AD-H, 20% J = 1.45,8.29 Hz, 1H), 7.20 (d, J = 8.19 Hz, 1H), IPA 7.06 (d, J = 8.19 Hz, 1H),5.40-5.54 (m, 2H), 3.40- Peak 2 3.62 (m, 3H), 3.17-3.35 (m, 2H),2.29-2.42 (m, 1H), 2.01-2.26 (m, 1H), 1.95 (br s, 2H) 57 400 MHz 8.93(s, 1H), 8.31 (br d, J = 8.19 Hz, 1H), 7.48 (d, — — d₆- J = 8.19 Hz,1H), 7.35 (s, 1H), 7.24 (s, 1H), 5.53 (s, DMSO 2H), 3.39 (br d, J =11.09 Hz, 2H), 3.29 (br d, J = 12.44 Hz, 2H), 2.84 (br t, J = 10.37 Hz,1H), 2.57-2.78 (m, 2H), 1.77 (br dd, J = 3.89, 8.55 Hz, 1H), 1.65 (brdd, J = 4.20, 9.38 Hz, 1H), 1.40-1.61 (m, 1H), 1.05-1.21 (m, 1H) 58 400MHz 8.93 (s, 1H), 8.32 (d, J = 8.19 Hz, 1H), 7.52 (d, — — d₆- J = 8.19Hz, 1H), 7.36 (s, 1H), 7.26 (s, 1H), 5.58 (s, DMSO 2H), 4.24-4.47 (m,1H), 3.34-3.52 (m, 3H), 2.98- 3.10 (m, 1H), 2.78-2.95 (m, 2H), 2.05 (brt, J = 12.70 Hz, 1H), 1.84-1.99 (m, 1H), 1.64-1.83 (m, 1H) 59 400 MHz8.93 (s, 1H), 8.32 (d, J = 8.29 Hz, 1H), 7.52 (d, — — d₆- J = 8.09 Hz,1H), 7.35 (s, 1H), 7.26 (s, 1H), 5.57 (s, DMSO 2H), 4.64-4.86 (m, 2H),3.17-3.38 (m, 2H), 3.05- 3.17 (m, 1H), 2.93-3.02 (m, 1H), 2.82-2.93 (m,1H), 1.92-2.04 (m, 1H), 1.79 (br s, 1H) 60 400 MHz 8.89-8.96 (m, 1H),8.33 (d, J = 7.79 Hz, 1H), 7.56 — — d₆- (d, J = 8.29 Hz, 1H), 7.32-7.40(m, 1H), 7.28 (s, DMSO 1H), 5.54-5.66 (m, 2H), 3.34-3.46 (m, 2H), 3.15-3.26 (m, 1H), 2.96-3.14 (m, 2H), 2.16-2.31 (m, 1H), 1.87-2.08 (m, 2H),1.78-1.87 (m, 1H) 61 400 MHz 8.94 (s, 1H), 8.31 (dd, J = 2.07, 8.19 Hz,1H), 7.44 B Regis Whelk- d₆- (d, J = 8.29 Hz, 1H), 7.02 (d, J = 8.78 Hz,1H), 6.95 O s, s, 30% DMSO (t, J = 10.39 Hz, 1H), 5.50 (s, 2H), 3.33 (brd, methanol J = 11.82 Hz, 2H), 3.23 (br d, J = 12.23 Hz, 2H), Peak 22.66-2.87 (m, 2H), 2.54-2.63 (m, 1H), 1.73-1.90 (m, 1H), 1.60-1.72 (m,1H), 1.41-1.58 (m, 1H), 1.16 (br s, 1H) 62 400 MHz 8.93 (s, 1H), 8.31(dd, J = 1.97, 8.19 Hz, 1H), 7.48 B Regis Whelk- d₆- (d, J = 8.29 Hz,1H), 7.14 (dd, J = 1.92, 9.28 Hz, O s, s, 30% DMSO 1H), 6.85 (t, J =10.74 Hz, 1H), 5.50 (s, 2H), 3.34- methanol 3.44 (m, 4H), 2.73-2.91 (m,2H), 2.63 (dd, J = 9.07, Peak 1 11.87 Hz, 1H), 1.74-1.86 (m, 1H),1.62-1.74 (m, 1H), 1.43-1.60 (m, 1H), 1.11-1.28 (m, 1H) 63 400 MHz 8.93(s, 1H), 8.32 (dd, J = 2, 02, 8.24 Hz, 1H), 7.50 B Chiralcel OJ- d₆- (d,J = 8.19 Hz, 1H), 7.03 (d, J = 8.98 Hz, 1H), 6.98 H, 15% DMSO (t, J =10.69 Hz, 1H), 5.55 (s, 2H), 4.33-4.59 (m, methanol 1H), 3.69-4.05 (m,2H), 3.31-3.50 (m, 2H), 2.96- Peak 2 3.09 (m, 2H), 2.83 (dd, J = 9.02,12.54 Hz, 1H), 2.02-2.12 (m, 1H), 1.67-1.79 (m, 1H) 64 400 MHz 8.92 (s,1H), 8.32 (dd, J = 1.76, 8.19 Hz, 1H), 7.52 B Chiralcel OJ- d₆- (d, J =8.29 Hz, 1H), 7.16 (dd, J = 1.92, 9.28 Hz, H, 15% DMSO 1H), 6.87 (t, J =10.73 Hz, 1H), 5.55 (s, 2H), 4.26- methanol 4.49 (m, 1H), 3.36-3.45 (m,2H), 3.02-3.10 (m, Peak 1 1H), 2.88-2.99 (m, 1H), 2.82 (dd, J = 8.60,12.44 Hz, 1H), 1.92-2.15 (m, 1H), 1.66-1.86 (m, 3H) 65 400 MHz 8.94 (s,1H), 8.31 (dd, J = 1, 97, 8.19 Hz, 1H), 7.48 B Phenomenex d₆- (d, J =8.19 Hz, 1H), 7.02 (d, J = 8.08 Hz, 1H), 6.96 Lux DMSO (t, J = 10.40 Hz,1H), 5.49-5.58 (m, 2H), 4.63-4.83 Cellulose-2, (m, 1H), 3.04-3.26 (m,3H), 2.84-2.97 (m, 2H), 20% 1.75-2.01 (m, 2H), 1.65 (br s, 2H) methanolPeak 2 66 400 MHz 8.92 (s, 1H), 8.31 (dd, J = 1.87, 8.19 Hz, 1H), 7.51 BPhenomenex d₆- (d, J = 8.19 Hz, 1H), 7.16 (dd, J = 1.92, 9.28 Hz, LuxDMSO 1H), 6.86 (t, J = 10.73 Hz, 1H), 5.49-5.59 (m, 2H), Cellulose-2,4.81 (br s, 1H), 3.10-3.29 (m, 3H), 2.90-3.02 (m, 20% 2H), 1.81-2.03 (m,2H), 1.63 (br s, 2H) methanol Peak 1 67 400 MHz 8.92 (s, 1H), 8.32 (dd,J = 1.97, 8.19 Hz, 1H), 7.55 B Phenomenex d₆- (d, J = 8.19 Hz, 1H), 7.19(dd, J = 1.81, 9.28 Hz, Lux DMSO 1H), 6.89 (t, J = 10.66 Hz, 1H), 5.59(s, 2H), 3.33- Cellulose-2, 3.56 (m, 2H), 3.10-3.26 (m, 2H), 2.98-3.10(m, 20% 1H), 2.21-2.32 (m, 1H), 2.00-2.14 (m, 1H), 1.78 methanol (br s,2H) Peak 1 68 400 MHz 8.93 (s, 1H), 8.33 (dd, J = 2.18, 8.19 Hz, 1H),7.74 B Chiralpak d₆- (d, J = 1.04 Hz, 1H), 7.48-7.58 (m, 3H), 5.61 (s,AD-H, 25% DMSO 2H), 4.25-4.47 (m, 1H), 3.38-3.57 (m, 2H), 3.04- methanol3.17 (m, 1H), 2.80-2.92 (m, 2H), 1.99-2.12 (m, Peak 1 1H), 1.60-1.79 (m,3H) 69 400 MHz 8.92 (s, 1H), 8.33 (dd, J = 2.18, 8.19 Hz, 1H), 7.91 BChiralpak d₆- (d, J = 1.14 Hz, 1H), 7.54 (d, J = 8.19 Hz, 1H), 7.45AD-H, 25% DMSO (dd, J = 1.45, 8.29 Hz, 1H), 7.33 (d, J = 8.29 Hz,methanol 1H), 5.62 (s, 2H), 4.27-4.48 (m, 1H), 3.36-3.56 Peak 2 (m, 2H),3.01-3.14 (m, 1H), 2.79-2.96 (m, 2H), 1.96-2.22 (m, 2H), 1.81-1.96 (m,1H), 1.66-1.81 (m, 1H) 70 400 MHz 8.96 (d, J = 1.45 Hz, 1H), 8.28 (dd, J= 2.18, 8.19 — — d₆- Hz, 1H), 7.43 (d, J = 7.67 Hz, 1H), 7.32 (d, J =8.29 DMSO Hz, 1H), 6.98-7.13 (m, 3H), 5.47 (s, 2H), 3.35 (br dd, J =3.42, 11.71 Hz, 2H), 3.14-3.30 (m, 1H), 2.67-2.89 (m, 2H), 2.58 (dd, J =9.02, 11.71 Hz, 1H), 1.73-1.87 (m, 1H), 1.60-1.72 (m, 1H), 1.42- 1.60(m, 2H), 1.08-1.22 (m, 1H) 71 400 MHz 9.06 (br s, 3H), 8.88-9.00 (m,1H), 8.37 (dd, B Chiralcel OD- d₆- J = 2.18, 8.19 Hz, 1H), 7.67 (d, J =8.19 Hz, 1H), H, 15% IPA DMSO 7.38 (dd, J = 2.44, 9.17 Hz, 1H), 7.27(dd, J = 4.56, Peak 2 8.81 Hz, 1H), 7.05 (t, J = 9.27 Hz, 1H), 5.61-5.87(m, 2H), 3.96-4.12 (m, 1H), 3.90 (br d, J = 12.85 Hz, 1H), 3.42-3.54 (m,2H), 3.23-3.34 (m, 1H), 2.45-2.60 (m, 1H), 2.20-2.37 (m, 1H) 72 400 MHz8.94 (d, J = 1.45 Hz, 1H), 8.31 (dd, J = 2.18, 8.19 — — d₆- Hz, 1H),7.50 (t, J = 9.11 Hz, 1H), 7.45 (d, J = 8.50 DMSO Hz, 1H), 7.36 (dd, J =7.36, 10.78 Hz, 1H), 5.52 (s, 2H), 4.23-4.46 (m, 1H), 3.22-3.45 (m, 3H),2.81- 3.05 (m, 2H), 2.76 (dd, J = 8.60, 12.44 Hz, 1H), 1.87-2.12 (m,1H), 1.63-1.87 (m, 3H) 73 400 MHz 8.96 (dd, J = 0.73, 2.07 Hz, 1H), 8.29(dd, J = 2.18, — — d₆- 8.19 Hz, 1H), 7.45 (d, J = 7.54 Hz, 1H), 7.37 (d,DMSO J = 8.29 Hz, 1H), 7.00-7.13 (m, 3H), 5.51 (s, 2H), 4.63-4.84 (m,1H), 3.06-3.26 (m, 3H), 2.88-3.00 (m, 2H), 1.79-2.03 (m, 2H), 1.59 (brs, 2H) 74 400 MHz 8.90 (d, J = 1.45 Hz, 1H), 8.37-8.43 (m, 1H), 8.34 BChiralpak d₆- (br s, 2H), 7.85 (d, J = 8.19 Hz, 1H), 7.46-7.54 (m, AD-H,30% DMSO 2H), 7.22-7.34 (m, 2H), 5.93 (s, 2H), 3.83-4.11 isopropanol (m,4H), 3.60-3.75 (m, 1H), 2.95-3.15 (m, 2H), Peak 1 1.91 (td, J = 4.13,8.22 Hz, 1H), 1.03 (dd, J = 5.29, 7.77 Hz, 1H), 0.52 (t, J = 4.87 Hz,1H) 75 400 MHz 8.90 (d, J = 1.97 Hz, 1H), 8.39 (s, 1H), 8.34 (br s, BChiralpak d₆- 3H), 7.86 (d, J = 8.29 Hz, 1H), 7.47-7.53 (m, 2H), AD-H,30% DMSO 7.22-7.34 (m, 2H), 5.93 (s, 2H), 4.04-4.13 (m, isopropanol 1H),3.83-4.02 (m, 3H), 3.63-3.73 (m, 1H), 2.95- Peak 2 3.20 (m, 2H), 1.91(td, J = 4.09, 8.19 Hz, 1H), 0.98- 1.07 (m, 1H), 0.52 (t, J = 4.87 Hz,1H) 76 400 MHz 8.89-8.97 (m, 1H), 8.50 (br s, 2H), 8.41 (dd, BPhenomenex d₆- J = 2.13, 8.24 Hz, 1H), 7.91 (d, J = 8.29 Hz, 1H), LuxDMSO 7.49 (d, J = 8.71 Hz, 2H), 7.23-7.34 (m, 2H), 5.88- Cellulose-2,6.16 (m, 2H), 4.21 (br dd, J = 6.22, 10.88 Hz, 1H), 25% 3.87 (br dd, J =7.26, 10.26 Hz, 1H), 3.42-3.77 (m, isopropanol 3H), 2.97-3.16 (m, 1H),2.82-2.94 (m, 1H), 1.71- w/0.2% DEA 2.04 (m, 3H), 1.42-1.64 (m, 1H) Peak1 77 400 MHz 8.92 (d, J = 1.45 Hz, 1H), 8.47 (br d, J = 1.35 Hz, BPhenomenex d₆- 3H), 8.41 (dd, J = 2.07, 8.19 Hz, 1H), 7.89 (br d, LuxDMSO J = 8.09 Hz, 1H), 7.49 (d, J = 8.09 Hz, 2H), 7.23- Cellulose-2,7.34 (m, 2H), 5.86-6.14 (m, 2H), 4.10-4.29 (m, 25% 1H), 3.75-4.02 (m,1H), 3.54-3.73 (m, 3H), 2.97- isopropanol 3.07 (m, 1H), 2.82-2.92 (m,1H), 1.74-1.99 (m, w/0.2% DEA 3H), 1.41-1.65 (m, 1H) Peak 4 78 400 MHz8.82 (s, 1H), 8.20-8.29 (m, 1H), 7.79 (d, J = 8.19 B Phenomenex d₄- Hz,1H), 7.28-7.50 (m, 4H), 5.90 (s, 2H), 3.92- Lux methanol 4.12 (m, 3H),3.69-3.76 (m, 1H), 3.55-3.63 (m, Cellulose-2, 1H), 3.02-3.17 (m, 1H),2.89-2.96 (m, 2H), 2.28- 25% 2.38 (m, 1H), 2.18 (dtd, J = 5.34, 7.78,13.31 Hz, isopropanol 1H), 1.73-1.85 (m, 1H), 1.60-1.72 (m, 1H) w/0.2%DEA Peak 2 79 400 MHz 8.82 (d, J = 1.45 Hz, 1H), 8.26 (dd, J = 2.07,8.19 B Phenomenex d₄- Hz, 1H), 7.78 (d, J = 8.09 Hz, 1H), 7.29-7.50 (m,Lux methanol 4H), 5.85-5.93 (m, 2H), 4.05-4.12 (m, 1H), 3.91-Cellulose-2, 4.01 (m, 2H), 3.55-3.77 (m, 2H), 3.01-3.18 (m, 25% 1H),2.92 (ddt, J = 4.28, 4.51, 8.41 Hz, 1H), 2.28- isopropanol 2.37 (m, 1H),2.13-2.23 (m, 1H), 1.74-1.85 (m, w/0.2% DEA 1H), 1.58-1.71 (m, 1H), 1.43(s, 1H) Peak 3 80 400 MHz 8.91 (d, J = 1.45 Hz, 1H), 8.40 (dd, J = 2.18,8.19 B Chiralpak IC, d₆- Hz, 1H), 8.28 (br s, 3H), 7.82 (d, J = 8.09 Hz,1H), 40% DMSO 7.48 (dd, J = 3.21, 7.77 Hz, 2H), 7.28-7.33 (m, 1H),isopropanol 7.25 (d, J = 7.37 Hz, 1H), 5.94 (d, J = 3.73 Hz, 2H), w/0.2%DEA 3.87-3.94 (m, 1H), 3.64-3.86 (m, 3H), 2.88 (br t, Peak 1 J = 6.27Hz, 2H), 2.61-2.70 (m, 1H), 2.16 (br d, J = 6.22 Hz, 1H), 1.82-1.91 (m,1H) 81 400 MHz 8.91 (d, J = 1.45 Hz, 1H), 8.36-8.43 (m, 1H), 8.33 BChiralpak IC, d₆- (br s, 2H), 7.82 (d, J = 8.19 Hz, 1H), 7.49 (dd, 40%DMSO J = 3.84, 7.67 Hz, 2H), 7.21-7.36 (m, 2H), 5.89- isopropanol 5.97(m, 2H), 3.65-3.93 (m, 5H), 3.47-3.51 (m, w/0.2% DEA 1H), 2.79-2.96 (m,2H), 2.61-2.72 (m, 1H), 2.12- Peak 2 2.21 (m, 1H), 1.82-1.92 (m, 1H) 82500 MHz 8.92 (s, 1H), 8.54 (br s, 2H), 8.33 (br d, J = 7.79 Hz, B —DMSO- 1H), 7.72 (s, 1H), 7.57 (br s, 2H), 5.62 (q, J = 17.82 d₆ Hz, 2H),5.01-5.20 (m, 1H), 3.59-3.63 (m, 1H), 3.20-3.31 (m, 2H), 3.08 (br t, J =10.96 Hz, 1H), 2.08 (br s, 1H), 1.86-2.03 (m, 1H) 83 400 MHz 8.93 (s,1H), 8.40 (br s, 2H), 8.33 (dd, J = 1.66, 8.09 B — DMSO- Hz, 1H),7.48-7.57 (m, 2H), 7.38 (dd, J = 7.46, d₆ 10.26 Hz, 1H), 5.50-5.63 (m,2H), 5.00-5.20 (m, 1H), 3.50 (br s, 1H), 3.24-3.33 (m, 1H), 3.15-3.23(m, 1H), 3.02-3.14 (m, 1H), 1.87-2.12 (m, 2H) 84 400 MHz 8.90-8.97 (m,1H), 8.86 (br s, 2H), 8.34 (br d, B — DMSO- J = 8.29 Hz, 1H), 7.53-7.63(m, 2H), 7.40 (dd, d₆ J = 7.31, 10.52 Hz, 1H), 5.54-5.73 (m, 2H), 3.92-4.21 (m, 2H), 3.65-3.78 (m, 2H), 3.33 (br d, J = 7.05 Hz, 1H), 3.09-3.21(m, 1H), 2.15-2.32 (m, 1H) 85 500 MHz, 8.86-8.99 (m, 2H), 8.56 (d, J =2.21 Hz, 1H), 7.99 B — DMSO- (br d, J = 8.04 Hz, 1H), 7.47-7.59 (m, 2H),7.25 (br d₆ s, 2H), 7.15-7.23 (m, 1H), 5.50-5.67 (m, 2H), 4.06-4.14 (m,1H), 3.78-3.95 (m, 3H), 3.25-3.39 (m, 1H), 2.25-2.35 (m, 1H) 86 500 MHz,8.55 (d, J = 2.21 Hz, 1H), 8.47 (br s, 2H), 7.96 (dd, B — DMSO- J =2.34, 8.43 Hz, 1H), 7.50 (d, J = 7.78 Hz, 1H), d₆ 7.40 (br d, J = 7.40Hz, 1H), 7.09-7.22 (m, 3H), 5.43-5.58 (m, 2H), 5.04-5.22 (m, 1H),3.72-3.84 (m, 2H), 3.62-3.69 (m, 2H), 3.36-3.43 (m, 2H), 3.19-3.28 (m,1H), 2.04-2.16 (m, 1H) 87 500 MHz, 8.93 (d, J = 1.95 Hz, 1H), 8.81 (brs, 2H), 8.34 (dd, B — DMSO- J = 2.08, 8.17 Hz, 1H), 7.59 (d, J = 8.17Hz, 1H), d₆ 6.98-7.06 (m, 2H), 5.56-5.75 (m, 2H), 4.00 (dt, J = 3.63,5.51 Hz, 1H), 3.73 (br d, J = 12.33 Hz, 1H), 3.38 (br d, J = 12.33 Hz,1H), 3.27-3.34 (m, 1H), 3.10-3.19 (m, 1H), 2,37-2.44 (m, 1H), 2.16-2,33(m, 1H) 88 500 MHz 8.84 (d, J = 1.82 Hz, 1H), 8.15 (dd, J = 2.08, 8.30 IYMC d₄- Hz, 1H), 7.40-7.52 (m, 2H), 6.91-7.00 (m, 2H), Amyose SA, MeOH5.47-5.62 (m, 2H), 3.34-3.54 (m, 2H), 3.08-3.28 Methanol (m, 3H),2.21-2.36 (m, 1H), 2.00-2.21 (m, 1H) THF (70:30) 40%; peak 1 89 500 MHz8.94 (d, J = 1.56 Hz, 1H), 8.33 (dd, J = 1.95, 8.17 — d₆- Hz, 1H), 7.57(d, J = 8.56 Hz, 1H), 7.43 (t, J = 7.27 DMSO Hz, 2H), 7.18 (t, J = 7.91Hz, 1H), 5.58-5.69 (m, 2H), 3.34-3.28 (m, 3H), 3.02-3.13 (m, 2H), 2.18-2.33 (m, 1H), 1.97-2.13 (m, 1H) 90 600 MHz 8.95 (d, J = 1.56 Hz, 1H),8.34 (dd, J = 2.02, 8.25 — — d₆- Hz, 1H), 7.54 (d, J = 8.10 Hz, 1H),7.44 (d, J = 8.10 DMSO Hz, 1H), 7.41 (d, J = 7.79 Hz, 1H), 7.16 (t, J =7.94 Hz, 1H), 5.54-5.67 (m, 2H), 4.26-4.45 (m, 1H), 3.38-3.50 (m, 2H),3.01-3.10 (m, 1H), 2.79-2.92 (m, 2H), 2.00-2.13 (m, 1H), 1.66-1.80 (m,1H) 91 600 MHz 8.95 (d, J = 1.25 Hz, 1H), 8.33 (dd, J = 2.02, 8.25 — —d₆- Hz, 1H), 7.53 (d, J = 8.41 Hz, 1H), 7.43 (d, J = 8.10 DMSO Hz, 1H),7.40 (d, J = 7.79 Hz, 1H), 7.16 (t, J = 7.79 Hz, 1H), 5.54-5.66 (m, 2H),4.66-4.84 (m, 1H), 3.30 (br d, J = 3.74 Hz, 1H), 3.25 (td, J = 4.05,12.77 Hz, 1H), 3.08-3.16 (m, 1H), 2.97-3.05 (m, 1H), 2.83-2.95 (m, 1H),1.95-2.02 (m, 1H), 1.78-1.94 (m, 1H) 92 500 MHz 8.79 (d, J = 1.30 Hz,1H), 8.15 (dd, J = 2.08, 8.04 B Separated by d₄- Hz, 1H), 8.05 (d, J =1.82 Hz, 1H), 7.77 (d, J = 2.08 flash MeOH Hz, 1H), 7.54 (d, J = 8.04Hz, 1H), 5.52-5.64 (m, chromatography 2H), 4.30-4.48 (m, 1H), 3.68-3.75(m, 1H), 3.58- 3.67 (m, 1H), 3.14-3.23 (m, 1H), 2.94-3.06 (m, 2H),2.08-2.19 (m, 1H), 1.75-1.87 (m, 1H) 93 500 MHz 8.83 (d, J = 1.30 Hz,1H), 8.17-8.22 (m, 2H), 7.66 B Separated by d₄- (d, J = 2.34 Hz, 1H),7.54 (d, J = 8.30 Hz, 1H), 5.54 flash MeOH (s, 2H), 4.32-4.50 (m, 1H),3.64-3.75 (m, 1H), chromatography 3.52-3.64 (m, 1H), 3.15-3.27 (m, 1H),3.02-3.10 (m, 1H), 2.99 (dd, J = 8.56, 12.20 Hz, 1H), 2.06- 2.23 (m,1H), 1.78-1.92 (m, 1H) 94 500 MHz 8.80 (d, J = 1.82 Hz, 1H), 8.19 (d, J= 2.34 Hz, 1H), B Separated by d₄- 8.12 (dd, J = 2.34, 8.04 Hz, 1H),7.62 (d, J = 2.08 flash MeOH Hz, 1H), 7.41 (d, J = 8.04 Hz, 1H), 5.49(s, 2H), chromatography 4.34-4.50 (m, 1H), 3.70-3.77 (m, 1H), 3.58-3.66(m, 1H), 3.21 (ddd, J = 2.47, 10.19, 13.04 Hz, 1H), 3.06-3.15 (m, 1H),2.99-3.05 (m, 1H), 2.10-2.20 (m, 1H), 1.82-1.92 (m, 1H), 1.43 (s, 9H) 95500 MHz 8.86 (d, J = 1.30 Hz, 1H), 8.13 (dd, J = 2.08, 8.30 — — d₄- Hz,1H), 7.51 (d, J = 7.79 Hz, 1H), 7.31 (d, J = 8.30 MeOH Hz, 1H),7.16-7.22 (m, 1H), 7.09-7.16 (m, 2H), 5.51 (s, 2H), 3.57-3.63 (m, 1H),3.37-3.51 (m, 2H), 3.01-3.10 (m, 1H), 2.76-2.92 (m, 2H), 1.95- 2.03 (m,1H), 1.57-1.72 (m, 1H) 96 500 MHz 8.85 (d, J = 1.56 Hz, 1H), 8.13 (dd, J= 2.08, 8.30 — — d₄- Hz, 1H), 7.51 (d, J = 8.04 Hz, 1H), 7.31 (d, J =8.56 MeOH Hz, 1H), 7.16-7.21 (m, 1H), 7.09-7.15 (m, 2H), 5.51 (s, 2H),3.56-3.64 (m, 1H), 3.37-3.51 (m, 2H), 3.06 (dt, J = 2.60, 12.07 Hz, 1H),2.78-2.92 (m, 2H), 1.99 (br dd, J = 2.85, 13.23 Hz, 1H), 1.60- 1.71 (m,1H) 97 500 MHz 8.86 (s, 1H), 8.08 (dd, J = 2.08, 8.30 Hz, 1H), 7.37 — —d₄- (d, J = 7.79 Hz, 1H), 7.23 (d, J = 8.04 Hz, 1H), 7.07- MeOH 7.13 (m,2H), 7.01 (t, J = 7.53 Hz, 1H), 5.55 (s, 2H), 3.68 (s, 2H), 3.49-3.61(m, 6H), 2.15 (t, J = 6.88 Hz, 2H) 98 500 MHz 8.83 (d, J = 1.30 Hz, 1H),8.26 (dd, J = 2.08, 8.04 B Chiralcel OD- d₄- Hz, 1H), 7.80 (d, J = 8.30Hz, 1H), 7.51 (d, J = 8.04 H, 25% MeOH Hz, 1H), 7.33-7.47 (m, 3H), 5.95(d, J = 19.72 Hz, MeOH 1H), 5.80 (br d, J = 18.68 Hz, 1H), 4.17-4.37 (m,Peak 1 3H), 3.97-4.10 (m, 2H), 3.80 (br t, J = 8.95 Hz, 1H), 3.68-3.76(m, 1H), 3.55 (dd, J = 1.95, 13.36 Hz, 1H), 3.32-3.46 (m, 2H) 99 500 MHz8.83 (s, 1H), 8.27 (dd, J = 1.82, 8.30 Hz, 1H), 7.80 B Chiralcel OD- d₄-(d, J = 8.56 Hz, 1H), 7.51 (d, J = 8.04 Hz, 1H), 7.38- H, 25% MeOH 7.47(m, 2H), 7.35 (br d, J = 8.04 Hz, 1H), 5.94 (d, MeOH J = 18.68 Hz, 1H),5.80 (br d, J = 18.68 Hz, 1H), Peak 2 4.18-4.36 (m, 3H), 3.95-4.06 (m,2H), 3.80 (br t, J = 8.30 Hz, 1H), 3.67-3.76 (m, 1H), 3.50-3.59 (m, 1H),3.33-3.47 (m, 2H) 100 500 MHz 8.87 (d, J = 1.30 Hz, 1H), 8.11 (dd, J =2.08, 8.04 B Chiralcel OD- d₄- Hz, 1H), 7.38 (d, J = 7.79 Hz, 1H), 7.28(d, J = 8.30 H, 20% MeOH Hz, 1H), 7.07-7.16 (m, 2H), 6.99-7.06 (m, 1H),MeOH 5.63 (d, J = 18.42 Hz, 1H), 5.48 (d, J = 18.42 Hz, Peak 1 1H), 3.93(dd, J = 2.72, 11.81 Hz, 1H), 3.64-3.75 (m, 3H), 3.48-3.63 (m, 2H), 3.43(dd, J = 8.95, 10.77 Hz, 1H), 2.84-3.00 (m, 3H) 101 500 MHz 8.87 (d, J =1.56 Hz, 1H), 8.11 (dd, J = 2.08, 8.30 B Chiralcel OD- d₄- Hz, 1H), 7.38(d, J = 8.04 Hz, 1H), 7.28 (d, J = 8.30 H, 20% MeOH Hz, 1H), 7.07-7.16(m, 2H), 6.99-7.06 (m, 1H), MeOH 5.63 (d, J = 18.42 Hz, 1H), 5.48 (d, J= 18.68 Hz, Peak 2 1H), 3.93 (dd, J = 2.60, 11.94 Hz, 1H), 3.64-3.74 (m,3H), 3.47-3.62 (m, 2H), 3.43 (dd, J = 8.95, 10.77 Hz, 1H), 2.85-2.99 (m,3H) 102 500 MHz 8.79-8.88 (m, 1H), 8.12 (dd, J = 2.21, 8.17 Hz, 1H), FChiralpak d₄- 7.50 (d, J = 7.79 Hz, 1H), 7.38 (d, J = 8.30 Hz, 1H),AD-H, 60% MeOH 7.06-7.21 (m, 3H), 5.48-5.65 (m, 2H), 3.46 (d, MeOH w/ J= 11.94 Hz, 1H), 3.35-3.42 (m, 1H), 3.17-3.23 (m, 0.2% DEA 1H),3.03-3.12 (m, 1H), 2.12 (ddd, J = 4.41, 11.35, Peak 1 13.30 Hz, 1H),1.89-2.01 (m, 1H), 1.70-1.80 (m, 1H), 1.59-1.68 (m, 1H) 103 500 MHz 8.85(d, J = 1.56 Hz, 1H), 8.13 (dd, J = 2.08, 8.30 F Chiralpak d₄- Hz, 1H),7.51 (d, J = 7.79 Hz, 1H), 7.39 (d, J = 8.04 AD-H, 60% MeOH Hz, 1H),7.08-7.22 (m, 3H), 5.51-5.66 (m, 2H), MeOH w/ 3.47 (d, J = 12.20 Hz,1H), 3.37-3.43 (m, 1H), 3.21 0.2% DEA (br d, J = 12.20 Hz, 1H),3.04-3.11 (m, 1H), 2.07- Peak 2 2.18 (m, 1H), 1.90-2.01 (m, 1H),1.72-1.81 (m, 1H), 1.58-1.70 (m, 1H) 104 500 MHz 8.86 (d, J = 1.56 Hz,1H), 8.12 (dd, J = 2.08, 8.30 B Chiralcel OD- d₄- Hz, 1H), 7.51 (d, J =7.78 Hz, 1H), 7.32 (d, J = 8.30 H, 25% MeOH Hz, 1H), 7.06-7.23 (m, 3H),5.48-5.62 (m, 2H), iPrOH w/ 3.54 (d, J = 10.90 Hz, 1H), 3.37 (d, J =10.90 Hz, 0.2% DEA 1H), 3.24-3.28 (m, 1H), 3.08-3.22 (m, 2H), 3.04 Peak1 (br d, J = 11.94 Hz, 1H), 1.79-1.90 (m, 1H), 1.66- 1.77 (m, 1H), 1.61(ddd, J = 4.28, 9.02. 13.43 Hz, 1H), 1.44-1.54 (m, 1H) 105 500 MHz 8.86(d, J = 1.30 Hz, 1H), 8.12 (dd, J = 2.08, 8.04 B Chiralcel OD- d₄- Hz,1H), 7.51 (d, J = 7.78 Hz, 1H), 7.33 (d, J = 8.04 H, 25% MeOH Hz, 1H),7.07-7.22 (m, 3H), 5.51-5.62 (m, 2H), iPrOH w/ 3.54 (d, J = 11.16 Hz,1H), 3.37 (d, J = 11.16 Hz, 0.2% DEA 1H), 3.24-3.28 (m, 1H), 3.09-3.22(m, 2H), 3.01- Peak 2 3.08 (m, 1H), 1.79-1.90 (m, 1H), 1.67-1.77 (m,1H), 1.62 (ddd, J = 4.41, 9.02, 13.56 Hz, 1H), 1.46- 1.56 (m, 1H) 106600 MHz 8.94 (d, J = 1.48 Hz, 1H), 8.33 (dd, J = 2.10, 8.17 B SFC: DMSO-Hz, 1H), 7.58-7.63 (m, 2H), 7.51 (d, J = 8.25 Hz, Chiralcel OD- d₆ 1H),7.42 (d, J = 8.21 Hz, 1H), 5.61-5.68 (m, 2H), H, 15% 4.75-4.83 (m, 1H),4.68-4.73 (m, 1H), 3.28-3.32 methanol. (m, 3H), 3.24 (td, J = 4.03,12.81 Hz, 1H), 3.05- 3.19 (m, 2H), 2.86-3.04 (m, 3H), 2.57-2.65 (m, 1H),2.33-2.48 (m, 1H), 1.92-2.01 (m, 1H), 1.77- 1.91 (m, 1H) 107 600 MHz9.00 (d, J = 1.32 Hz, 1H), 8.39 (dd, J = 2.10, 8.25 B SFC: DMSO- Hz,1H), 7.84 (s, 1H), 7.58 (d, J = 8.17 Hz, 1H), Chiralcel OD- d₆ 7.37-7.45(m, 2H), 5.63-5.72 (m, 2H), 4.83-4.90 H, 15% (m, 1H), 4.76-4.81 (m, 1H),3.33-3.37 (m, 2H), methanol. 3.30 (td, J = 3.99, 12.65 Hz, 1H),3.13-3.25 (m, 2H), 2.95-3.11 (m, 2H), 2.01-2.09 (m, 1H), 1.87- 2.00 (m,1H) 108 600 MHz 8.94 (d, J = 1.40 Hz, 1H), 8.34 (dd, J = 2.14, 8.21 BSFC: DMSO- Hz, 1H), 7.62 (s, 1H), 7.63 (d, J = 6.89 Hz, 1H), ChiralcelOD- d₆ 7.56 (d, J = 8.17 Hz, 1H), 7.44 (d, J = 8.47 Hz, 1H), H, 15%5.65-5.73 (m, 2H), 3.18-3.26 (m, 1H), 2.98-3.12 methanol. (m, 2H),2.17-2.29 (m, 1H), 1.89-2.07 (m, 1H), 1.79 (br s, 2H) 109 600 MHz 8.94(dd, J = 0.66, 2.06 Hz, 1H), 8.34 (dd, J = 2.14, B SFC: DMSO- 8.21 Hz,1H), 7.80 (s, 1H), 7.56 (d, J = 8.17 Hz, Chiralcel OD- d₆ 1H), 7.38 (dd,J = 1.21, 8.45 Hz, 1H), 7.33 (d, H, 15% J = 8.41 Hz, 1H), 5.58-5.69 (m,2H), 3.37-3.44 (m, methanol. 1H), 3.20-3.30 (m, 1H), 3.07-3.18 (m, 1H),2.99- 3.06 (m, 1H), 2.21-2.31 (m, 1H), 1.96-2.11 (m, 2H), 1.92 (br s,1H) 110 600 MHz 8.94 (d, J = 1.48 Hz, 1H), 8.49 (br s, 3H), 8.36 (dd, BSFC: DMSO- J = 2.06, 8.21 Hz, 1H), 7.55 (br d, J = 8.10 Hz, 1H),Phenomenex d₆ 7.33 (s, 1H), 7.10 (d, J = 8.25 Hz, 1H), 6.99 (br d, Lux J= 8.17 Hz, 1H), 5.55-5.63 (m, 2H), 4.69-4.81 (m, Cellulose-2, 1H),4.24-4.38 (m, 1H), 3.81 (br d, J = 12.38 Hz, 25% 1H), 3.61 (br s, 1H),3.54 (br d, J = 12.69 Hz, 1H), methanol. 3.10-3.21 (m, 2H), 2.51-2.54(m, 9H), 2.37 (s, 3H), 2.21 (br t, J = 9.81 Hz, 1H), 1.82-1.90 (m, 1H)111 600 MHz 8.40 (br s, 1H), 8.27 (dd, J = 2.06, 8.21 Hz, 1H), B SFC:DMSO- 7.47 (br d, J = 8.17 Hz, 1H), 6.94-6.98 (m, 1H), Phenomenex d₆5.44-5.54 (m, 1H), 4.76 (dt, J = 4.94, 9.17 Hz, 1H), Lux 3.90-4.72 (m,3H), 3.69 (br d, J = 12.61 Hz, 1H), Cellulose-2, 3.52 (br s, 1H), 3.42(br d, J = 12.38 Hz, 1H), 2.98- 25% 3.12 (m, 1H), 2.42-2.52 (m, 5H),2.23 (s, 2H), 2.11 methanol. (br t, J = 9.81 Hz, 1H), 1.72-1.81 (m, 1H)112 600 MHz 8.95 (dd, J = 0.70, 2.02 Hz, 1H), 8.31 (dd, J = 2.14, B SFC:DMSO- 8.21 Hz, 1H), 7.41 (s, 1H), 7.41 (d, J = 6.67 Hz, Phenomenex d₆1H), 7.29 (s, 1H), 5.43-5.54 (m, 2H), 4.34-4.43 Lux (m, 1H), 4.26-4.34(m, 1H), 3.25-3.38 (m, 11H), Cellulose-2, 2.96-3.05 (m, 1H), 2.85-2.91(m, 1H), 2.76 (dd, 20% J = 8.60, 12.50 Hz, 1H), 2.34 (s, 3H), 1.94-2.08(m, methanol 2H), 1.65-1.83 (m, 1H) 113 600 MHz 8.96 (s, 1H), 8.31 (dd,J = 2.14, 8.21 Hz, 1H), 7.38- B SFC: DMSO- 7.53 (m, 2H), 7.15 (s, 1H),5.38-5.53 (m, 2H), Phenomenex d₆ 4.25-4.43 (m, 1H), 3.38-3.40 (m, 1H),3.29-3.34 Lux (m, 1H), 2.97-3.05 (m, 1H), 2.84-2.92 (m, 1H),Cellulose-2, 2.76 (dd, J = 8.56, 12.53 Hz, 1H), 2.30 (s, 3H), 20%1.98-2.09 (m, 1H), 1.63-1.80 (m, 3H) methanol 114 600 MHz 8.95 (s, 1H),8.30 (dd, J = 2.14, 8.21 Hz, 1H), 7.37 B SFC: DMSO- (d, J = 8.33 Hz,1H), 7.31 (d, J = 6.93 Hz, 1H), 7.03 Phenomenex d₆ (d, J = 9.89 Hz, 1H),5.44-5.52 (m, 2H), 4.35-4.41 Lux (m, 1H), 4.26-4.34 (m, 1H), 3.19-3.33(m, 1H), Cellulose-2, 2.93-3.02 (m, 1H), 2.78-2.93 (m, 1H), 2.74 (dd,20% J = 8.64, 12.46 Hz, 1H), 2.25 (d, J = 1.48 Hz, 3H), methanol.2.10-2.23 (m, 1H), 1.95-2.09 (m, 2H), 1.66-1.83 (m, 1H) 115 600 MHz8.92-8.98 (m, 1H), 8.30 (d, J = 7.92 Hz, 1H), 7.31- B SFC: DMSO- 7.44(m, 2H), 7.22 (d, J = 10.43 Hz, 1H), 7.03 (d, Phenomenex d₆ J = 7.01 Hz,1H), 5.36-5.51 (m, 2H), 4.35-4.41 (m, Lux 1H), 4.26-4.34 (m, 1H),3.26-3.44 (m, 1H), 2.85- Cellulose-2, 3.02 (m, 1H), 2.69-2.81 (m, 2H),2.23-2.27 (m, 20% 1H), 2.21 (d, J = 1.56 Hz, 3H), 1.92-2.08 (m, 1H),methanol. 1.60-1.92 (m, 1H) 116 600 MHz 8.98 (d, J = 1.63 Hz, 1H), 8.31(dd, J = 2.14, 8.21 B — DMSO- Hz, 1H), 7.44 (d, J = 7.63 Hz, 1H), 7.38(d, J = 8.25 d₆ Hz, 1H), 7.07-7.15 (m, 2H), 6.94-7.04 (m, 1H), 5.44-5.50(m, 2H), 3.38-3.48 (m, 1H), 3.23-3.32 (m, 1H), 2.82-2.91 (m, 1H),2.52-2.62 (m, 1H), 2.43-2.49 (m, 1H), 2.11 (s, 3H), 1.80-1.88 (m, 1H),1.68 (td, J = 3.67, 13.14 Hz, 1H), 1.50-1.61 (m, 1H), 1.11-1.23 (m, 1H)117 600 MHz 8.96 (s, 1H), 8.34 (dd, J = 2.14, 8.21 Hz, 1H), 7.52 — —DMSO- (d, J = 7.98 Hz, 2H), 7.27 (s, 1H), 7.15-7.20 (m, d₆ 1H), 7.12 (d,J = 7.93 Hz, 1H), 7.10 (s, 1H), 5.62 (d, J = 17.75 Hz, 1H), 5.55 (d, J =17.75 Hz, 1H), 3.68 (br d, J = 11.83 Hz, 1H), 3.34 (br s, 1H), 3.19-3.28(m, 2H), 3.01 (br t, J = 9.42 Hz, 1H), 2.51-2.61 (m, 3H), 1.98-2.06 (m,1H), 1.83 (dt, J = 2.88, 6.50 Hz, 1H), 1.53-1.67 (m, 2H) 118 600 MHz8.94 (s, 1H), 8.33 (dd, J = 2.14, 8.21 Hz, 1H), 7.47 B SFC: DMSO- (dd, J= 2.18, 8.33 Hz, 2H), 7.05-7.09 (m, 2H), 6.95 Chiralcel OD- d₆ (d, J =8.98 Hz, 1H), 5.51-5.58 (m, 2H), 4.47-4.56 H, 15% (dt, J = 4.59, 8.68Hz, 1H), 3.43-3.57 (m, 1H), 3.37- methanol. 3.43 (m, 1H), 3.10-3.23 (m,1H), 2.96-3.03 (m, 1H), 2.87 (dd, J = 9.26, 12.61 Hz, 1H), 2.05-2.12 (m,1H), 1.70-1.79 (m, 1H) 119 600 MHz 8.95 (s, 1H), 8.32 (dd, J = 2.14,8.21 Hz, 1H), 7.45 B SFC: DMSO- (d, J = 8.33 Hz, 1H), 7.22-7.30 (m, 1H),7.10-7.18 Chiralcel OD- d₆ (m, 1H), 6.87 (dd, J = 2.34, 8.56 Hz, 1H),5.50-5.57 H, 15% (m, 2H), 4.43 (dt, J = 4.59, 8.25 Hz, 1H), 3.40-3.49methanol. (m, 1H), 3.37-3.40 (m, 1H), 2.91-3.07 (m, 1H), 2.81 (dd, J =8.80, 12.53 Hz, 1H), 2.57-2.65 (m, 1H), 2.01-2.11 (m, 1H), 1.68-1.78 (m,1H) 120 600 MHz 8.95 (d, J = 1.95 Hz, 1H), 8.29 (dd, J = 2.10, 8.25 — —DMSO- Hz, 1H), 7.33 (d, J = 8.25 Hz, 1H), 6.96 (t, J = 8.02 d₆ Hz, 1H),6.73 (d, J = 8.02 Hz, 1H), 6.67 (d, J = 8.08 Hz, 1H), 5.44-5.53 (m, 2H),4.28-4.34 (m, 1H), 3.89 (s, 3H), 3.24-3.42 (m, 1H), 2.85-3.01 (m, 2H),2.75 (dd, J = 8.64, 12.46 Hz, 1H), 1.98-2.16 (m, 1H), 1.95 (br s, 1H),1.69-1.86 (m, 1H) 121 600 MHz 8.94 (s, 1H), 8.30 (dd, J = 1.95, 8.17 Hz,1H), 7.43 — — DMSO- (d, J = 8.25 Hz, 1H), 6.91-7.03 (m, 3H), 5.48-5.57d₆ (m, 2H), 4.86-4.78(m, 1H), 3.64-3.78 (m, 1H), 3.48-3.63 (m, 1H),3.06-3.17 (m, 1H), 2.99 (br t, J = 11.44 Hz, 1H), 2.46-2.49 (m, 1H),2.14-2.23 (m, 1H), 1.82-1.91 (m, 1H) 122 600 MHz 9.03 (d, J = 1.40 Hz,1H), 8.71-8.78 (m, 1H), 8.28 B SFC: DMSO- (br s, 1H), 7.86 (br s, 1H),7.67 (s, 1H), 7.60 (d, Chiralpak d₆ J = 8.33 Hz, 1H), 7.42 (d, J = 8.47Hz, 1H), 5.64- AD-H, 25% 5.77 (m, 2H), 4.75-71 (m, 1H), 3.30-3.31 (m,2H), methanol 3.07-3.17 (m, 1H), 2.86-3.02 (m, 1H), 2.28-2.45 (m, 1H),1.93-2.12 (m, 1H), 1.78-1.93 (m, 1H) 123 600 MHz 9.03 (d, J = 1.32 Hz,1H), 8.75 (d, J = 1.32 Hz, 1H), B SFC: DMSO- 8.27 (s, 1H), 7.86 (br s,1H), 7.77 (s, 1H), 7.34- Chiralpak d₆ 7.41 (m, 2H), 5.68 (d, J = 1.79Hz, 2H), 4.77-4.72 AD-H, 25% (m, 1H), 3.22-3.32 (m, 1H), 3.09-3.20 (m,1H), methanol 2.89-3.04 (m, 2H), 1.95-2.05 (m, 1H), 1.80-1.94 (m, 1H),1.76 (br s, 1H) 124 600 MHz 8.92 (s, 1H), 8.33 (dd, J = 2.14, 8.21 Hz,1H), 7.70 B SFC: DMSO- (s, 1H), 7.52 (d, J = 8.47 Hz, 1H), 7.49 (s, 1H),5.60 Chiralpak d₆ (s, 2H), 4.35-4.35 (m, 1H), 3.38-3.51 (m, 1H), AD-H,25% 2.98-3.08 (m, 1H), 2.82-2.90 (m, 1H), 2.78 (dd, methanol J = 8.64,12.53 Hz, 1H), 2.00-2.09 (m, 1H), 1.77 (br s, 1H), 1.63-1.74 (m, 1H) 125600 MHz 8.94 (s, 1H), 8.33 (dd, J = 2.14, 8.21 Hz, 1H), 7.62 B SFC:DMSO- (s, 1H), 7.57 (s, 1H), 7.55 (d, J = 8.35 Hz, 1H), Chiralpak d₆5.54-5.63 (m, 2H), 4.39-4.27 (m, 1H), 3.37-3.46 AD-H, 25% (m, 2H),2.98-3.09 (m, 1H), 2.82-2.91 (m, 1H), methanol 2.78 (dd, J = 8.60, 12.57Hz, 1H), 1.98-2.09 (m, 1H), 1.63-1.80 (m, 1H) 126 600 MHz 8.93 (s, 1H),8.34 (dd, J = 2.14, 8.21 Hz, 1H), 7.75 B SFC: DMSO- (s, 1H), 7.72 (s,1H), 7.55 (d, J = 8.25 Hz, 1H), Chiralcel OJ- d₆ 5.63-5.71 (m, 2H),4.37-4.28(m, 1H), 3.36-3.51 H, 10% (m, 2H), 3.04-3.11 (m, 1H), 2.79-2.88(m, 2H), methanol 2.00-2.08 (m, 1H), 1.62-1.78 (m, 1H) 127 600 MHz ¹HNMR (600 MHz, DMSO-d₆) δ 8.93 (d, J = 1.40 B SFC: DMSO- Hz, 1H), 8.34(dd, J = 2.10, 8.17 Hz, 1H), 7.88 (s, Chiralcel OJ- d₆ 1H), 7.63 (s,1H), 7.57 (d, J = 8.17 Hz, 1H), 5.60- H, 10% 5.67 (m, 2H),4.37-4.42-4.29 (m, 1H), 3.36-3.45 methanol. (m, 1H), 3.14-3.29 (m, 1H),3.00-3.09 (m, 1H), 2.77-2.89 (m, 2H), 1.95-2.08 (m, 1H), 1.64-1.81 (m,1H) 128 600 MHz 8.90-8.99 (m, 1H), 8.26-8.35 (m, 1H), 7.52-7.44 — —DMSO- (d, J = 7.66 Hz, 1H), 7.33 (d, J = 8.30 Hz, 1H), 7.23- d₆ 7.29 (m,1H), 7.00-7.19 (m, 1H), 6.99-7.19 (m, 1H), 5.76-5.42 (m, 2H), 2.98-3.15(m, 2H), 2.72- 2.91 (m, 2H), 2.69-2.65 (s, 1H), 2.22-2.39 (m, 1H), 1.71(br d, J = 6.36 Hz, 1H), 1.69 (br d, J = 5.19 Hz, 1H), 1.42-1.62 (m,6H), 1.38 (s, 1H). 129 600 MHz 8.97 (s, 1H), 8.30 (dd, J = 2.14, 8.21Hz, 1H), 7.45 B SFC: DMSO- (d, J = 7.79 Hz, 1H), 7.33 (d, J = 8.17 Hz,1H), 7.18 Phenomenex d₆ (d, J = 7.79 Hz, 1H), 7.00-7.14 (m, 2H),5.47-5.60 Lux (m, 2H), 3.12-3.27 (m, 1H), 3.06 (br d, J = 11.99Cellulose-2, Hz, 1H), 2.88-3.01 (m, 2H), 2.56-2.64 (m, 1H), 30%2.51-2.56 (m, 1H), 1.64-1.73 (m, 2H), 1.46-1.59 methanol (m, 1H),1.21-1.41 (m, 7H) 130 600 MHz 8.97 (d, J = 1.71 Hz, 1H), 8.30 (dd, J =2.14, 8.21 B SFC: DMSO- Hz, 1H), 7.45 (d, J = 7.55 Hz, 1H), 7.33 (d, J =8.17 Phenomenex d₆ Hz, 1H), 7.18 (d, J = 7.86 Hz, 1H), 7.02-7.12 (m, Lux2H), 5.47-5.58 (m, 2H), 3.12-3.26 (m, 1H), 3.06 Cellulose-2, (br d, J =12.07 Hz, 1H), 2.87-3.01 (m, 2H), 2.56- 30% 2.63 (m, 1H), 2.52-2.55 (m,1H), 1.63-1.73 (m, methanol 2H), 1.46-1.58 (m, 1H), 1.21-1.41 (m, 7H)131 600 MHz 8.96 (s, 1H), 8.29 (dd, J = 2.14, 8.21 Hz, 1H), 7.44 B SFC:DMSO- (d, J = 7.71 Hz, 1H), 7.35 (d, J = 8.25 Hz, 1H), 7.06- Phenomenexd₆ 7.12 (m, 2H), 6.93-7.04 (m, 1H), 5.41-5.51 (m, Lux 2H), 4.10 (br s,1H), 3.75 (td, J = 2.88, 10.98 Hz, Cellulose-2, 1H), 3.69 (q, J = 3.58Hz, 1H), 3.37-3.49 (m, 1H), 30% 3.01-3.21 (m, 2H), 2.80-2.94 (m, 2H),2.43-2.49 methanol. (m, 1H), 1.81 (br s, 1H), 1.67-1.79 (m, 1H) 132 600MHz 8.96 (s, 1H), 8.29 (dd, J = 2.14, 8.21 Hz, 1H), 7.45 B SFC: DMSO-(d, J = 7.97 Hz, 1H), 7.37 (d, J = 8.25 Hz, 1H), 7.07- Phenomenex d₆7.13 (m, 2H), 6.98-7.06 (m, 1H), 5.44-5.52 (m, Lux 2H), 4.11 (br s, 1H),3.80 (td, J = 2.86, 11.25 Hz, Cellulose-2, 1H), 3.74 (br d, J = 3.11 Hz,1H), 3.44-3.54 (m, 30% 1H), 3.14-3.21 (m, 2H), 2.94-3.12 (m, 2H), 2.51-methanol. 2.62 (m, 1H), 1.83 (br s, 1H), 1.69-1.80 (m, 1H) 133 600 MHz9.04 (s, 1H), 8.70 (s, 1H), 7.85 (m, 1H), 7.52 (dd, — — DMSO- J = 7.47,10.98 Hz, 1H), 7.50 (br dd, J = 7.32, 10.35 d₆ Hz, 1H), 7.10-7.25 (m,1H), 5.57 (s, 2H), 4.45- 4.60 (m, 1H), 3.62-3.70 (m, 1H), 3.36-3.46 (m,1H), 2.97 (br t, J = 11.21 Hz, 1H), 2.75 (br dd, J = 10.12, 12.30 Hz,1H), 2.33-2.46 (m, 1H), 2.10- 2.20 (m, 1H), 1.78-1.86 (m, 1H) 134 600MHz 9.03 (d, J = 1.37 Hz, 1H), 8.74-8.75 (dd, J = 1.37, — — DMSO- 5.87Hz, 1H), 8.25 (br d, J = 3.97 Hz, 1H), 7.83 (br d₆ s, 1H), 7.5-7.68 (s,1H), 7.60 (d, J = 8.32 Hz, 1H), 7.36-7.44 (m, 2H), 5.72 (s, 1H), 5.68(s, 1H), 4.36- 4.45 (m, 1H), 3.38-3.54 (m, 2H), 3.02-3.13 (m, 1H),2.80-2.95 (m, 2H), 1.99-2.16 (m, 1H), 1.67- 1.78 (m, 1H) 135 600 MHz8.98 (d, J = 1.56 Hz, 1H), 8.30 (dd, J = 2.14, 8.21 B SFC: DMSO- Hz,1H), 7.44 (d, J = 7.79 Hz, 1H), 7.33 (d, J = 8.25 Phenomenex d₆ Hz, 1H),7.15 (d, J = 7.86 Hz, 1H), 7.10 (t, J = 7.76 Lux Hz, 1H), 7.03 (t, J =7.58 Hz, 1H), 5.54-5.60 (m, Cellulose-2, 1H), 5.44-5.52 (m, 1H),3.15-3.27 (m, 1H), 3.04-3.13 (m, 2H), 40% 2.75-2.89 (m, 3H), 2.56-2.64(m, 1H), 1.65-1.76 (m, 1H), methanol 1.54-1.63 (m, 2H), 1.42-1.52 (m,4H), 1.27-1.41 (m, 1H) 136 600 MHz 8.98 (dd, J = 0.74, 2.06 Hz, 1H),8.30 (dd, J = 2.14, B SFC: DMSO- 8.21 Hz, 1H), 7.44 (d, J = 7.55 Hz,1H), 7.33 (d, Phenomenex d₆ J = 8.33 Hz, 1H), 7.15 (d, J = 7.86 Hz, 1H),7.10 (dt, Lux J = 1.17, 7.59 Hz, 1H), 7.00-7.06 (m, 1H), 5.57 (d,Cellulose-2, J = 17.91 Hz, 1H), 5.48 (d, J = 17.91 Hz, 1H), 3.15- 40%3.27 (m, 1H), 3.02-3.14 (m, 2H), 2.75-2.90 (m, methanol. 3H), 2.56-2.64(m, 1H), 1.65-1.76 (m, 1H), 1.54- 1.63 (m, 2H), 1.42-1.52 (m, 4H),1.27-1.40 (m, 1H) 137 600 MHz 8.96 (d, J = 1.48 Hz, 1H), 8.29 (dd, J =2.14, 8.21 B SFC: DMSO- Hz, 1H), 7.38 (d, J = 8.17 Hz, 1H), 7.05 (s,1H), Chiralcel OJ- d₆ 7.01 (d, J = 8.55 Hz, 1H), 6.67 (dd, J = 2.41,8.72 H, 15% Hz, 1H), 5.46-5.55 (m, 2H), 3.73 (s, 1H), 3.08-3.24 (m, 2H),methanol 2.97 (br dd, J = 9.03, 11.29 Hz, 1H), 2.52-2.57 (m, 1H),2.19-2.28 (m, 1H), 1.93-2.09 (m, 1H), 1.83 (br s, 1H) 138 600 MHz 8.96(d, J = 1.63 Hz, 1H), 8.29 (dd, J = 2.10, 8.17 B SFC: DMSO- Hz, 1H),7.39 (d, J = 8.10 Hz, 1H), 7.36 (d, J = 8.52 Chiralcel OJ- d₆ Hz, 1H),6.78 (s, 1H), 6.74 (d, J = 8.78 Hz, 1H), H, 15% 5.53 (s, 2H), 3.66-3.69(m, 1H), 3.05-3.17 (m, methanol 2H), 2.90-2.96 (m, 1H), 2.17-2.26 (m,1H), 1.97- 2.07 (m, 1H), 1.75 (br s, 1H) 139 600 MHz 8.95 (d, J = 1.95Hz, 1H), 8.30-8.35 (m, 1H), 7.60 B SFC: DMSO- (s, 1H), 7.59 (d, J =10.87 Hz, 1H), 7.50 (d, J = 8.17 Chiralcel OD- d₆ Hz, 1H), 7.42 (dd, J =1.32, 8.33 Hz, 1H), 5.56-5.63 H, 15% (m, 2H), 3.49 (br dd, J = 3.23,12.03 Hz, 2H), 2.87- methanol w/ 2.94 (m, 1H), 2.57-2.69 (m, 1H),2.42-2.48 (m, 0.2% DEA 1H), 2.11 (s, 3H), 1.81-1.87 (m, 1H), 1.64-1.71(m, 1H), 1.48-1.56 (m, 1H), 1.15-1.28 (m, 1H) 140 600 MHz 8.95 (d, J =1.63 Hz, 1H), 8.33 (dd, J = 2.10, 8.25 B SFC: DMSO- Hz, 1H), 7.75 (s,1H), 7.50 (d, J = 8.25 Hz, 1H), Chiralcel OD- d₆ 7.29-7.40 (m, 2H),5.51-5.60 (m, 2H), 3.48 (br dd, H, 15% J = 3.23, 12.03 Hz, 2H),2.86-2.95 (m, 1H), 2.62 methanol w/ (dd, J = 9.03, 12.07 Hz, 1H),2.43-2.48 (m, 0.2% DEA 1H), 2.09-2.13 (m, 3H), 1.81-1.88 (m, 1H), 1.69(td, J = 3.79, 13.29 Hz, 1H), 1.51-1.59 (m, 1H), 1.16-1.28 (m, 1H) 141600 MHz 8.97 (s, 1H), 8.28 (dd, J = 2.02, 8.17 Hz, 1H), 7.43 — — DMSO-(d, J = 7.79 Hz, 1H), 7.32 (d, J = 8.25 Hz, 1H), 7.16 d_(s) (d, J = 7.79Hz, 1H), 7.09 (t, J = 7.24 Hz, 1H), 7.02 (t, J = 7.28 Hz, 1H), 5.47-5.57(m, 2H), 3.08-3.25 (m, 2H), 2.96 (br t, J = 8.95 Hz, 1H), 2.77-2.89 (m,2H), 1.73 (tdd, J = 4.41, 8.78, 13.23 Hz, 1H), 1.55 (td, J = 3.37, 6.50Hz, 2H), 1.29-1.48 (m, 2H), 0.93 (s, 1H) 142 500 MHz 8.95 (s, 1H), 8.36(br d, J = 8.19 Hz, 1H), 8.10 (br s, B SFC: DMSO- 3H), 7.56 (d, J = 8.19Hz, 1H), 7.15 (d, J = 8.81 Hz, Chiralpak IC, d₆ 1H), 7.07 (s, 1H), 6.81(br d, J = 8.91 Hz, 1H), 40% 5.52-5.65 (m, 2H), 3.77 (s, 3H), 3.58-3.75(m, isopropanol 1H), 3.34 (br d, J = 13.27 Hz, 2H), 3.21 (br dd, J =8.71, 12.13 Hz, 1H), 3.07 (br t, J = 9.23 Hz, 1H), 1.96 (br s, 1H), 1.83(br s, 1H), 1.58 (br s, 2H) 143 500 MHz 8.95 (s, 1H), 8.35 (d, J = 8.09Hz, 1H), 8.02 (br s, B SFC: DMSO- 3H), 7.52 (d, J = 8.29 Hz, 1H), 7.42(d, J = 8.50 Hz, Chiralpak IC, d₆ 1H), 6.83-6.89 (m, 2H), 5.51-5.66 (m,2H), 40% 3.48-3.67 (m, 1H), 3.34 (br s, 1H), 3.26 (br d, isopropanol J =13.48 Hz, 1H), 3.15 (br dd, J = 8.34, 12.39 Hz, 1H), 2.94-3.07 (m, 1H),1.94 (br s, 1H), 1.81 (br s, 1H), 1.56 (br s, 2H) 144 500 MHz 8.91 (d, J= 1.45 Hz, 1H), 8.41 (br s, 3H), 8.33 (dd, — — DMSO- J = 2.07, 8.19 Hz,1H), 7.55 (d, J = 8.29 Hz, 1H), d₆ 7.15-7.21 (m, 2H), 5.40-5.64 (2, 2H),4.72-4.84 (dt, J = 5.03, 9.36 Hz, 1H), 3.69-3.78 (m, 1H), 3.51 (br s,1H), 3.43 (br d, J = 12.54 Hz, 1H), 2.94-3.12 (m, 2H), 2.12-2.22 (m,1H), 1.73-1.88 (m, 1H) 145 500 MHz 8.94 (d, J = 1.55 Hz, 1H), 8.75 (brs, 3H), 8.37 (dd, B SFC: DMSO- J = 2.07, 8.19 Hz, 1H), 7.66 (br d, J =7.15 Hz, 1H), Chiralpak d₆ 7.21 (br d, J = 8.71 Hz, 1H), 7.08 (d, J =2.28 Hz, AD-H, 20% 1H), 6.84 (br d, J = 8.40 Hz, 1H), 5.60-5.76 (m,methanol 2H), 4.86-4.98 (m, 1H), 3.95 (br d, J = 6.95 Hz, 1H), 3.59-3.79(m, 1H), 3.28-3.52 (m, 1H), 3.00- 3.27 (m, 2H), 2.19-2.31 (m, 1H),1.79-1.91 (m, 1H) 146 500 MHz 8.94 (d, J = 1.45 Hz, 1H), 8.74 (br s,3H), 8.35 (dd, B SFC: DMSO- J = 2.07, 8.19 Hz, 1H), 7.60 (br d, J = 7.98Hz, 1H), Chiralpak d₆ 7.40-7.47 (m, J = 8.71 Hz, 1H), 6.93 (br s, 1H),AD-H, 20% 6.81-6.90 (m, J = 8.60 Hz, 1H), 5.59-5.76 (m, 2H), methanol4.81-5.01 (m, 1H), 3.86 (br d, J = 11.30 Hz, 1H), 3.59-3.79 (m, 1H),3.33-3.55 (m, 1H), 3.05-3.32 (m, 2H), 2.17-2.33 (m, 1H), 1.70-1.88 (m,1H) 147 500 MHz 8.87 (s, 2H), 8.05 (d, J = 8.19 Hz, 2H), 7.65 (d, B SFC:CDCl₃ J = 8.19 Hz, 2H), 5.84 (q, J = 6.57 Hz, 2H), 3.08 (s, ChiralcelOD- 6H), 1.78 (d, J = 6.63 Hz, 6H), 1.62 (br s, 3H), 1.44 H, 20% (br s,2H) methanol 148 500 MHz 8.97 (s, 1H), 8.59 (br s, 3H), 8.33 (dd, J =1.95, 8.17 B SFC: DMSO- Hz, 1H), 7.48 (br d, J = 7.91 Hz, 1H), 7.30-7.44(m, Chiralcel OD- d₆ 1H), 7.04-7.11 (m, 2H), 6.73 (d, J = 9.04 Hz, 1H),H, 20% 5.50-5.63 (m, 2H), 5.10-5.20 (br s, 1H), 3.70-3.80 methanol (m,1H), 3.44-3.65 (m, 2H), 3.10-3.29 (m, 2H), 1.93-2.16 (m, 2H). 149 500MHz 8.92 (s, 2H), 7.59 (d, J = 8.89 Hz, 1H), 7.52 (d, — — DMSO- J = 9.41Hz, 1H), 5.60 (d, J = 2.02 Hz, 2H), 4.73- d₆ 4.84 (m, 1H), 3.37-3.49 (m,1H), 3.11-3.17 (m, 1H), 2.97-3.08 (m, 2H), 2.51-2.55 (m, 1H), 1.93- 2.03(m, 1H), 1.78-1.91 (m, 1H). 150 500 MHz 8.91 (s, 2H), 7.55-7.63 (m, 2H),5.59-5.69 (m, 2H), B 0.1% NH4OH DMSO- 3.87-4.10 (m, 1H), 3.47 (br d, J =13.23 Hz, 1H), in ACN and d₆ 3.32-3.42 (m, 1H), 3.12-3.20 (m, 2H), 2.36(br d, water as J = 1.69 Hz, 1H), 2.26 (br s, 1H). mobile phase 151 500MHz 8.89 (s, 2H), 7.52-7.64 (m, 2H), 5.55-5.74 (m, B 0.1% NH4OH DMSO-2H), 3.83-3.95 (m, 1H), 3.32-3.50 (m, 2H), 3.10- in ACN and d₆ 3.22 (m,2H), 2.36-2.44 (m, 1H), 2.11-2.33 (m, 1H) water as mobile phase 152 500MHz 8.82-8.86 (m, 1H), 8.11-8.20 (m, 1H), 7.37-7.46 I YMC MeOD (m, 2H),7.21 (d, J = 1.82 Hz, 1H), 7.16 (dd, J = 1.82, Amyose SA, 8.30 Hz, 1H),5.49 (s, 2H), 3.58-3.63 (m, 1H), Methanol 3.42-3.53 (m, 2H), 3.05 (dt, J= 2.34, 12.07 Hz, THF (70:30) 1H), 2.80-2.91 (m, 2H), 1.95-2.02 (m, 1H),1.59- 40%; peak 1 1.70 (m, 1H) 153 500 MHz 8.84 (br s, 1H), 8.07-8.20(m, 1H), 7.37-7.50 (m, I YMC MeOD 2H), 7.06-7.27 (m, 2H), 5.52 (br s,2H), 3.93 (br s, Amyose SA, 1H), 3.34-3.43 (m, 2H), 3.01-3.16 (m, 2H),1.85 Methanol (br d, J = 3.37 Hz, 2H) THF (70:30) 40%; peak 1 154 400MHz 7.77-7.83 (m, J = 7.98 Hz, 2H), 7.48 (d, J = 7.67 Hz, — — d₆- 1H),7.29-7.36 (m, J = 7.98 Hz, 2H), 7.03-7.19 (m, DMSO 3H), 5.47 (s, 2H),3.35-3.41 (m, 1H), 3.26-3.30 (m, 1H), 3.11-3.24 (m, 2H), 2.94-3.05 (m,1H), 2.19-2.34 (m, 1H), 2.01-2.16 (m, 1H), 1.76 (br s, 2H) 155 400 MHz8.54 (br d, J = 3.01 Hz, 2H), 7.86 (d, J = 8.29 Hz, — — d₆- 2H), 7.60(d, J = 7.52 Hz, 1H), 7.44-7.53 (m, DMSO J = 8.19 Hz, 2H), 7.23-7.39 (m,3H), 5.66 (br d, J = 9.95 Hz, 2H), 4.04 (br d, J = 9.95 Hz, 1H), 3.72-3.80 (m, 1H), 3.57-3.64 (m, 1H), 3.31-3.53 (m, 2H), 3.01-3.29 (m, 2H),1.96-2.08 (m, 1H), 1.47- 1.64 (m, 1H) 156 600 MHz 7.79-7.84 (m, J = 8.41Hz, 2H), 7.26-7.32 (m, B SFC: DMSO- J = 8.41 Hz, 2H), 7.18 (dd, J =2.18, 9.26 Hz, 1H), Chiralcel OD- d₆ 6.91 (t, J = 10.35 Hz, 1H), 5.43(s, 2H), 4.39-4.38 H, 15% (m, 1H), 3.39-3.51 (m, 1H), 3.36-3.14-3.28 (m,methanol. 1H), 3.04-3.13 (m, 1H), 2.92-3.03 (m, 1H), 2.84 (dd, J = 8.60,12.65 Hz, 1H), 1.94-2.13 (m, 1H), 1.74-1.91 (m, 1H) 157 600 MHz δ7.79-7.84 (m, 2H), 7.28-7.33 (m, J = 8.49 Hz, B SFC: DMSO- 2H), 7.08(dd, J = 2.22, 8.84 Hz, 1H), 6.99 (dt, Chiralcel OJ- d₆ J = 2.18, 10.59Hz, 1H), 5.41-5.48 (m, 2H), 4.28- H, 15% 4.36 (m, 1H), 3.37-3.43 (m,1H), 2.99-3.06 (m, methanol 1H), 2.93 (tdd, J = 4.16, 7.88, 14.31 Hz,1H), 2.79 (dd, J = 8.60, 12.50 Hz, 1H), 2.01-2.13 (m, 1H), 1.66-1.80 (m,1H) 158 600 MHz 7.81-7.84 (m, J = 8.25 Hz, 2H), 7.78 (s, 1H), 7.43- BSFC: DMSO- 7.58 (m, 2H), 7.28-7.33 (m, 2H), 5.51 (s, 2H), Chiralpak d₆4.39-4.36 (m, 1H), 3.49-3.54 (m, 1H), 3.40-3.48 AD-H, 25% (m, 1H),3.03-3.17 (m, 1H), 2.73-2.94 (m, 1H), methanol 1.93-2.11 (m, 1H), 1.82(br s, 1H), 1.63-1.79 (m, 1H), 159 600 MHz 7.94 (s, 1H), 7.78-7.84 (m, J= 8.25 Hz, 2H), 7.47 B SFC: DMSO- (dd, J = 1.01, 8.25 Hz, 1H), 7.36 (d,J = 8.33 Hz, Chiralpak d₆ 1H), 7.26-7.32 (m, J = 8.17 Hz, 2H), 5.47-5.56(m, AD-H, 25% 2H), 4.42-4.34 (dt, J = 4.32, 8.19 Hz, 1H), 3.44- methanol3.52 (m, 1H), 3.38-3.43 (m, 1H), 3.15-3.28 (m, 1H), 3.04-3.14 (m, 1H),2.80-2.97 (m, 2H), 2.03- 2.12 (m, 1H), 1.70-1.88 (m, 1H) 160 600 MHz7.76-7.85 (m, 3H), 7.46-7.65 (m, 2H), 7.29-7.38 B SFC: DMSO- (m, 2H),5.54 (s, 2H), 3.85-4.05 (m, 1H), 3.35- Chiralpak d₆ 3.46 (m, 1H),3.21-3.35 (m, 1H), 3.03-3.20 (m, AD-H, 25% 1H), 2.54-2.79 (m, 1H),2.18-2.32 (m, 1H), 1.98- methanol 2.14 (m, 1H), 161 600 MHz 7.96 (d, J =1.17 Hz, 1H), 7.81 (d, J = 8.43 Hz, 2H), B SFC: DMSO- 7.48 (dd, J =1.49, 8.24 Hz, 1H), 7.29-7.38 (m, 3H), Chiralpak d₆ 5.48-5.57 (m, 2H),3.34-3.47 (m, 1H), 3.20-3.30 AD-H, 25% (m, 1H), 3.10-3.19 (m, 1H),2.96-3.09 (m, 1H), methanol 2.17-2.32 (m, 1H), 1.99-2.15 (m, 1H), 1.79(br d, J = 19.33 Hz, 1H) 162 400 MHz 7.80 (d, J = 8.29 Hz, 2H), 7.43 (d,J = 7.46 Hz, 1H), — — d₆- 7.30 (d, J = 8.29 Hz, 2H), 7.15 (d, J = 7.88Hz, 1H), DMSO 6.98-7.11 (m, 2H), 5.39 (s, 2H), 3.57 (s, 1H), 3.38 (brdd, J = 3.42, 11.82 Hz, 1H), 3.20-3.28 (m, 1H), 2.78-2.91 (m, 2H), 2.63(dd, J = 9.12, 11.82 Hz, 1H), 2.08-2.28 (m, 1H), 1.78-1.87 (m, 1H),1.65- 1.75 (m, 1H), 1.49-1.63 (m, 1H) 163 500 MHz 7.81 (d, J = 8.30 Hz,2H), 7.45 (d, J = 7.53 Hz, 1H), — — d₆- 7.32 (d, J = 8.30 Hz, 2H),7.07-7.18 (m, 2H), 6.98- DMSO 7.07 (m, 1H), 5.47 (s, 2H), 3.38-3.48 (m,1H), 3.05-3.17 (m, 2H), 2.79-2.93 (m, 1H), 1.83 (br s, 1H), 1.60-1.74(m, 1H), 1.41-1.54 (m, 1H), 0.94 (d, J = 6.75 Hz, 3H) 164 600 MHz 7.81(d, J = 8.10 Hz, 2H), 7.29 (d, J = 7.78 Hz, 1H), — — d₆- 7.25 (d, J =8.10 Hz, 2H), 7.14 (d, J = 7.79 Hz, 1H), DMSO 7.03 (t, J = 7.63 Hz, 1H),6.93 (t, J = 7.63 Hz, 1H), 5.51 (s, 2H), 3.51-3.59 (m, 2H), 3.42 (d, J =9.65 Hz, 1H), 3.18 (s, 1H), 3.14 (d, J = 9.65 Hz, 1H), 2.43 (d, J = 4.36Hz, 1H), 1.77-1.85 (m, 1H), 1.49- 1.56 (m, 1H), 0.96 (s, 3H) 165 600 MHz7.82 (d, J = 8.10 Hz, 2H), 7.21-7.37 (m, 8H), 7.17 — — d₆- (d, J = 7.79Hz, 1H), 7.04-7.08 (m, 1H), 6.95 (t, DMSO J = 7.47 Hz, 1H), 5.49-5.58(m, 2H), 3.94 (dd, J = 7.79, 9.65 Hz, 1H), 3.73 (dd, J = 6.85, 9.34 Hz,1H), 3.66 (t, J = 9.19 Hz, 1H), 3.42 (q, J = 7.16 Hz, 1H), 3.18 (d, J =4.67 Hz, 1H), 3.06 (q, J = 7.79 Hz, 1H), 1.72 (br s, 2H) 166 600 MHz7.82 (d, J = 8.10 Hz, 2H), 7.25-7.32 (m, 3H), 7.11 — — d₆- (d, J = 8.10Hz, 1H), 7.03 (t, J = 7.47 Hz, 1H), 6.92 DMSO (t, J = 7.63 Hz, 1H), 5.50(s, 2H), 3.57-3.66 (m, 2H), 3.44-3.51 (m, 2H), 3.14 (dd, J = 4.83, 9.50Hz, 1H), 1.95 (qd, J = 6.40, 12.26 Hz, 1H), 1.61 (qd, J = 6.34, 12.42Hz, 1H) 167 400 MHz 7.80 (d, J = 8.29 Hz, 2H), 7.43 (d, J = 7.46 Hz,1H), — — d₆- 7.30 (d, J = 8.29 Hz, 2H), 7.15 (d, J = 7.88 Hz, 1H), DMSO6.98-7.11 (m, 2H), 5.39 (s, 2H), 3.57 (s, 1H), 3.38 (br dd, J = 3.42,11.82 Hz, 1H), 3.20-3.28 (m, 1H), 2.78-2.91 (m, 2H), 2.63 (dd, J = 9.12,11.82 Hz, 1H), 2.08-2.28 (m, 1H), 1.78-1.87 (m, 1H), 1.65- 1.75 (m, 1H),1.49-1.63 (m, 1H) 168 500 MHz Mixture of diasteromers: 7.80 (br d, J =7.79 Hz, — — d₆- 2H), 7.27 (br dd, J = 7.91, 17.52 Hz, 3H), 7.13 (brDMSO d, J = 8.04 Hz, 1H), 7.02 (br t, J = 8.04 Hz, 1H), 6.93 (br d, J=7.53 Hz, 1H), 5.45-5.57 (m, 2H), 3.56- 3.79 (m, 1H), 3.09-3.19 (m, 2H),1.92-2.05 (m, 1H), 1.71-1.90 (m, 2H), 1.15-1.66 (m, 7H) 169 600 MHzMixture of diasteromers: 1.20-1.38 (m, 2 H), 1.56- — — DMSO- 1.71 (m, 2H), 1.88-2.07 (m, 1 H), 2.07-2.24 d₆ (m, 1 H), 2.52-2.59 (m, 1 H),2.62-2.72 (m, 1 H), 2.87 (q, J = 5.45 Hz, 1 H), 3.06 (br d, J = 10.12Hz, 1 H), 3.12-3.21 (m, 4 H), 3.23-3.31 (m, 2 H), 3.31-3.42 (m, 3 H),3.43-3.56 (m, 1 H), 3.61 (dd, J = 10.35, 4.59 Hz, 1 H), 5.47-5.55 (m, 2H), 6.92-7.01 (m, 1 H), 7.06 (t, J = 7.47 Hz, 1 H), 7.11- 7.19 (m, 1 H),7.22-7.31 (m, 2 H), 7.37 (d, J = 7.79 Hz, 1 H), 7.80 (d, J = 7.75 Hz, 2H) 170 400 MHz 8.45 (br s, 3H), 7.83 (d, J = 8.29 Hz, 2H), 7.49-7.58 — —MeOD (m, 1H), 7.36 (d, J = 8.09 Hz, 2H), 7.07-7.25 (m, 3H), 5.49 (s,2H), 4.71-4.91 (m, 1H), 3.75-3.84 (m, 1H), 3.61-3.73 (m, 1H), 3.36-3.48(m, 1H), 2.95-3.22 (m, 2H), 2.13-2.25 (m, 1H), 1.72-1.95 (m, 1H) 171 400MHz 8.34 (br d, J = 1.04 Hz, 3H), 7.82 (d, J = 8.29 Hz, — — MeOD 2H),7.46-7.56 (m, 1H), 7.34 (d, J = 8.29 Hz, 2H), 7.07-7.24 (m, 3H), 5.48(s, 2H), 5.03-5.21 (m, 1H), 3.76-3.87 (m, 1H), 3.52-3.61 (m, 1H), 3.31-3.42 (m, 1H), 3.07-3.28 (m, 2H), 1.89-2.16 (m, 2H) 172 400 MHz 8.37 (brs, 3H), 7.83 (d, J = 8.29 Hz, 2H), 7.48-7.56 — — MeOD (m, 1H), 7.35 (d,J = 8.29 Hz, 2H), 7.08-7.23 (m, 3H), 5.48 (s, 2H), 5.01-5.22 (m, 1H),3.74-3.91 (m, 1H), 3.57 (br dd, J = 4.04, 12.75 Hz, 1H), 3.40 (br d, J =11.20 Hz, 1H), 3.08-3.27 (m, 2H), 1.92- 2.18 (m, 2H) 173 400 MHz7.75-7.84 (m, 2H), 7.39-7.49 (m, 1H), 7.31 (d, — — MeOD J = 8.50 Hz,2H), 7.15-7.21 (m, 1H), 7.11 (dt, J = 1.35, 7.52 Hz, 1H), 7.02-7.07 (m,1H), 5.44 (s, 2H), 4.26-4.48 (m, 1H), 3.33-3.44 (m, 2H), 2.90- 3.09 (m,2H), 2.80 (dd, J = 8.71, 12.44 Hz, 1H), 2.00-2.16 (m, 1H), 1.70-1.87 (m,2H) 174 400 MHz 7.75-7.83 (m, 2H), 7.52-7.58 (m, 1H), 7.33-7.47 BPhenomenex MeOD (m, 5H), 5.68-5.89 (m, 2H), 4.00-4.23 (m, 4H), Lux3.42-3.65 (m, 2H), 2.48-2.64 (m, 1H), 2.24-2.47 Cellulose-2, (m, 1H) 25%MeOH, Peak 1 175 400 MHz 7.76-7.82 (m, 2H), 7.52-7.57 (m, 1H), 7.32-7.46B Phenomenex MeOD (m, 5H), 5.68-5.88 (m, 2H), 4.01-4.17 (m, 4H), Lux3.44-3.65 (m, 2H), 2.50-2.63 (m, 1H), 2.26-2.47 Cellulose-2, (m, 1H) 25%MeOH, Peak 2 176 400 MHz 7.75-7.82 (m, 2H), 7.50-7.55 (m, 1H), 7.39-7.46B Chiralpak MeOD (m, 3H), 7.33-7.37 (m, 2H), 5.65-5.86 (m, 2H), AD-H,30% 4.08 (dt, J = 7.05, 9.74 Hz, 1H), 3.91-4.01 (m, 2H), MeOH w/ 3.78(dd, J = 1.14, 10.26 Hz, 1H), 3.22 (d, J = 2.28 0.2% DEA, Hz, 2H),2.08-2.28 (m, 2H) Peak 1 177 400 MHz 7.74-7.83 (m, 2H), 7.50-7.55 (m,1H), 7.38-7.48 B Chiralpak MeOD (m, 3H), 7.31-7.38 (m, 2H), 5.66-5.86(m, 2H), AD-H, 30% 4.08 (dt, J = 6.95, 9.80 Hz, 1H), 3.89-4.01 (m, 2H),MeOH w/ 3.79 (dd, J = 1.14, 10.26 Hz, 1H), 3.23 (d, J = 2.70 0.2% DEA,Hz, 2H), 2.11-2.33 (m, 2H) Peak 2 178 400 MHz 7.66-7.74 (m, 2H),7.36-7.44 (m, 1H), 7.29 (d, — — MeOD J = 8.71 Hz, 2H), 7.00-7.16 (m,3H), 5.48-5.55 (m, 2H), 3.68 (dd, J = 7.15, 9.64 Hz, 1H), 3.59 (dd, J =6.12, 7.98 Hz, 2H), 2.70 (d, J = 7.26 Hz, 2H), 2.31-2.43 (m, 1H), 2.12(dd, J = 6.01, 12.23 Hz, 1H), 1.70 (dd, J = 8.29, 12.44 Hz, 1H),1.25-1.34 (m, 1H) 179 400 MHz 7.70 (d, J = 8.50 Hz, 2H), 7.36-7.43 (m,1H), 7.29 — — MeOD (d, J = 8.71 Hz, 2H), 6.99-7.17 (m, 3H), 5.46-5.59(m, 2H), 3.68 (dd, J = 7.26, 9.54 Hz, 1H), 3.54-3.64 (m, 2H), 2.69 (d, J= 7.26 Hz, 2H), 2.31-2.43 (m, 1H), 2.12 (d, J = 6.01 Hz, 1H), 1.61-1.78(m, 1H) 180 400 MHz 8.39 (br s, 3H), 7.87 (d, J = 8.29 Hz, 2H),7.53-7.62 — — d₆- (m, 1H), 7.50 (d, J = 8.29 Hz, 2H), 7.27-7.36 (m, DMSO1H), 7.22-7.26 (m, 2H), 5.53-5.75 (m, 2H), 3.86- 4.00 (m, 1H), 3.41-3.65(m, 3H), 3.28-3.36 (m, 1H), 3.00-3.17 (m, 2H), 1.89-2.09 (m, 2H), 1.51(br dd, J = 3.01, 12.96 Hz, 1H), 1.00 (d, J = 6.63 Hz, 3H) 181 400 MHz8.12-8.25 (m, 3H), 7.83 (d, J = 8.29 Hz, 2H), 7.48- — — d₆- 7.56 (m,1H), 7.35-7.40 (m, 2H), 7.10-7.26 (m, DMSO 3H), 5.49 (br d, J = 1.66 Hz,2H), 3.74-3.87 (m, 1H), 3.39 (br d, J = 12.65 Hz, 1H), 2.92-3.13 (m,3H), 1.64-1.82 (m, 2H), 1.32-1.47 (m, 1H), 1.04 (d, J = 6.22 Hz, 3H) 182400 MHz 8.12 (br d, J = 1.24 Hz, 3H), 7.83 (d, J = 8.50 Hz, — — d₆- 2H),7.48-7.58 (m, 1H), 7.31-7.40 (m, 2H), 7.17- DMSO 7.25 (m, 2H), 7.07-7.17(m, 1H), 5.47 (d, J = 1.66 Hz, 2H), 3.79 (br d, J = 9.74 Hz, 1H), 3.38(br d, J = 12.85 Hz, 1H), 2.89-3.18 (m, 3H), 1.58-1.85 (m, 2H), 1.40 (brd, J = 11.40 Hz, 1H), 1.04 (d, J = 6.22 Hz, 3H) 183 400 MHz 7.66-7.75(m, 2H), 7.39-7.47 (m, 1H), 7.27 (d, F Chiralpak MeOD J = 8.50 Hz, 2H),7.03-7.20 (m, 3H), 5.44-5.51 (m, AD-H, 20% 2H), 3.76 (d, J = 9.33 Hz,1H), 3.52-3.69 (m, 3H), MeOH w/ 2.90-3.00 (m, 1H), 2.80 (d, J = 13.48Hz, 1H), 1.49- 0.2% DEA, 1.58 (m, 1H), 0.84-0.95 (m, 1H), 0.69-0.79 (m,Peak 1 1H), 0.53 (t, J = 4.56 Hz, 1H) 184 400 MHz 7.65-7.75 (m, 2H),7.37-7.45 (m, 1H), 7.27 (d, F Chiralpak MeOD J = 8.29 Hz, 2H), 7.00-7.19(m, 3H), 5.48 (s, 2H), AD-H, 20% 3.76 (d, J = 9.33 Hz, 1H), 3.51-3.67(m, 3H), 2.94 MeOH w/ (br d, J = 13.48 Hz, 1H), 2.81 (s, 1H), 1.53 (td,0.2% DEA, J = 3.81, 7.93 Hz, 1H), 0.74 (dd, J = 5.18, 7.88 Hz, Peak 21H), 0.52 (t, J = 4.35 Hz, 1H) 185 400 MHz 7.70 (d, J = 8.50 Hz, 2H),7.38-7.44 (m, 1H), 7.31 F Chiralpak IC, MeOD (d, J = 8.29 Hz, 2H), 6.82(dd, J = 2.28, 8.71 Hz, 45% IPA w/ 1H), 6.71 (d, J = 2.28 Hz, 1H), 5.40(s, 2H), 3.38- 0.2% DEA, 3.46 (m, 1H), 3.21 (td, J = 4.17, 11.97 Hz,1H), peak 1 2.88-2.99 (m, 2H), 2.79 (dd, J = 8.91, 11.61 Hz, 1H),1.90-2.01 (m, 1H), 1.76-1.87 (m, 1H), 1.60- 1.73 (m, 1H), 1.28-1.40 (m,1H) 186 400 MHz 7.69 (d, J = 8.29 Hz, 2H), 7.27-7.34 (m, 2H), 7.07 FChiralpak IC, MeOD (d, J = 2.49 Hz, 1H), 7.00 (d, J = 8.71 Hz, 1H), 6.7545% IPA w/ (dd, J = 2.49, 8.71 Hz, 1H), 5.37 (s, 2H), 3.42-3.50 0.2%DEA, (m, 1H), 3.26 (br d, J = 12.23 Hz, 1H), 2.89-3.02 peak 2 (m, 2H),2.81 (dd, J = 8.91, 11.61 Hz, 1H), 1.93- 2.01 (m, 1H), 1.76-1.86 (m,1H), 1.59-1.75 (m, 1H), 1.28-1.41 (m, 1H) 442 500 MHz 9.05-9.18 (m, 2H),7.39-7.56 (m, 1H), 6.86-7.12 B Chiralpak d₄- (m, 2H), 5.51-5.68 (m, 2H),4.40-4.67 (m, 1H), OD-H, 15% MeOH 3.60-3.71 (m, 1H), 3.46-3.56 (m, 1H),3.28 (dd, IPA, Peak 1 J = 4.25, 8.40 Hz, 1H), 3.07-3.16 (m, 1H), 3.02(dd, J = 9.43, 12.34 Hz, 1H), 2.17-2.28 (m, 1H), 1.83- 1.98 (m, 1H) 443500 MHz 9.06-9.17 (m, 2H), 7.12-7.23 (m, 2H), 6.84-6.93 B Chiralpak d₄-(m, 1H), 5.57-5.67 (m, 2H), 4.36-4.57 (m, 1H), OD-H, 15% MeOH 3.58-3.69(m, 1H), 3.48-3.55 (m, 1H), 3.09-3.19 IPA, Peak 2 (m, 2H), 2.98 (dd, J =8.82, 12.46 Hz, 1H), 2.18- 2.27 (m, 1H), 1.81-1.96 (m, 1H) 444 500 MHz8.47 (s, 2H), 7.39-7.51 (m, 1H), 7.00 (dd, J = 2.34, B Chiralpak d₄-8.82 Hz, 1H), 6.95 (ddd, J = 2.47, 8.76, 9.80 Hz, OD-H, 15% MeOH 1H),5.36-5.51 (m, 2H), 4.60-4.80 (m, 1H), 3.89- MeOH, Peak 3.99 (m, 3H),3.77-3.89 (m, 1H), 3.61-3.71 (m, 1 1H), 3.57 (br dd, J = 4.28, 8.95 Hz,1H), 3.07-3.20 (m, 2H), 2.20-2.36 (m, 1H), 1.91-2.06 (m, 1H) 445 500 MHz7.37-7.42 (m, 1H), 6.71-6.87 (m, 2H), 5.06-5.16 B Chiralpak IC, d₄- (m,2H), 4.47-4.61 (m, 1H), 4.14-4.29 (m, 2H), 20% MeOH, MeOH 3.77-3.85 (m,3H), 3.48-3.55 (m, 1H), 3.02-3.09 Peak 1 (m, 1H), 2.94-3.00 (m, 1H),2.17-2.25 (m, 1H), 1.91-2.01 (m, 1H) 446 500 MHz 8.39-8.49 (m, 2H),7.10-7.24 (m, 2H), 6.77-6.93 B Chiralpak d₄- (m, 1H), 5.34-5.49 (m, 2H),4.35-4.57 (m, 1H), OD-H, 15% MeOH 3.70 (dtd, J = 1.82, 4.17, 12.42 Hz,1H), 3.51-3.60 MeOH, Peak (m, 1H), 3.13-3.23 (m, 2H), 3.01 (dd, J =8.82, 2 12.46 Hz, 1H), 2.14-2.28 (m, 1H), 1.78-1.99 (m, 1H) 447 500 MHz7.26-7.43 (m, 2H), 5.07-5.23 (m, 2H), 4.42-4.59 — — d₄- (m, 1H),4.12-4.24 (m, 1H), 3.61-3.70 (m, 1H), MeOH 3.44-3.56 (m, 1H), 3.19-3.27(m, 1H), 2.99-3.11 (m, 1H), 2.12-2.27 (m, 1H), 1.86-1.99 (m, 1H) 448 500MHz 7.37-7.40 (m, 1H), 6.79-6.87 (m, 2H), 5.03 (s, B Chiralpak d₄- 2H),4.47-4.57 (m, 1H), 4.38-4.61 (m, 2H), 3.83 OD-H, 15% MeOH (s, 3H),3.47-3.57 (m, 2H), 3.23 (s, 3H), 3.05-3.11 MeOH, Peak (m, 1H), 3.03 (s,3H), 2.96 (br dd, J = 8.95, 12.07 1 Hz, 1H), 2.15-2.28 (m, 2H),1.87-2.08 (m, 3H 449 500 MHz 7.37-7.42 (m, 1H), 6.71-6.87 (m, 2H),5.06-5.16 B Chiralpak IC, d₄- (m, 2H), 4.47-4.61 (m, 1H), 4.14-4.29 (m,2H), 15% MeOH, MeOH 3.77-3.85 (m, 3H), 3.48-3.55 (m, 1H), 3.02-3.09 Peak2 (m, 1H), 2.94-3.00 (m, 1H), 2.17-2.25 (m, 1H), 1.91-2.01 (m, 1H) 450500 MHz 7.11 (d, J = 8.82 Hz, 1H), 7.05 (d, J = 2.34 Hz, 1H), BChiralpak d₄- 6.80-6.85 (m, 1H), 5.01 (s, 2H), 4.44-4.58 (m, OD-H, 15%MeOH 1H), 3.82 (s, 3H), 3.53-3.60 (m, 1H), 3.41-3.47 MeOH, Peak (m, 2H),3.21 (s, 3H), 3.07-3.14 (m, 1H), 3.02 (s, 2 3H), 2.93-2.99 (m, 1H),2.18-2.28 (m, 1H), 1.91- 2.03 (m, 1H) 451 600 MHz 8.95 (d, J = 1.48 Hz,1H), 8.30 (dd, J = 2.10, 8.25 — — DMSO - Hz, 1H), 7.41 (td, J = 4.55,8.80 Hz, 2H), 7.09 (dd, d₆ J = 2.41, 9.19 Hz, 1H), 6.92 (t, J = 9.42 Hz,1H), 5.49 (s, 2H), 3.40 (br s, 1H), 3.24-3.36 (m, 3H), 3.17 (s, 1H),2.86-2.98 (m, 2H), 2.60-2.75 (m, 2H), 1.89-2.04 (m, 1H), 1.26-1.43 (m,1H) 452 600 MHz 8.94 (d, J = 1.40 Hz, 1H), 8.29 (dd, J = 2.14, 8.21 — —DMSO - Hz, 1H), 7.37 (d, J = 8.17 Hz, 1H), 6.69 (dd, d₆ J = 2.26, 8.88Hz, 1H), 6.59 (dd, J = 2.22, 12.18 Hz, 1H), 5.48 (s, 2H), 4.25-4.38 (m,1H), 3.89 (s, 3H), 3.22-3.29 (m, 1H), 2.84-2.98 (m, 2H), 2.62-2.76 (m,1H), 1.99-2.07 (m, 1H), 1.79 (br s, 1H), 1.64- 1.76 (m, 1H) 453 600 MHz8.90 (s, 1H), 8.34 (dd, J = 2.14, 8.21 Hz, 1H), 7.90 B Chiralpak DMSO -(d, J = 8.10 Hz, 1H), 7.64 (d, J = 8.35 Hz, 1H), 7.61 AD-H, 25% d₆ (d, J= 8.06 Hz, 1H), 5.64 (s, 2H), 4.30-4.44 (m, IPA, peak 1 1H), 3.59-3.68(m, 2H), 3.13-3.28 (m, 1H), 2.77- 2.90 (m, 2H), 1.99-2.08 (m, 1H),1.57-1.70 (m, 1H) 454 600 MHz 8.91 (s, 2H), 7.40 (dd, J = 4.90, 8.64 Hz,1H), 7.11 B Chiralpak DMSO - (dd, J = 2.49, 9.26 Hz, 1H), 6.91 (ddd, J =2.57, 8.68, AD-H, 25% d₆ 10.08 Hz, 1H), 5.45-5.52 (m, 2H), 3.27-3.29 (m,IPA, peak 1 3H), 2.86-2.97 (m, 2H), 2.61-2.71 (m, 2H), 1.96- 2.05 (m,1H), 1.58 (br s, 2H), 1.31-1.48 (m, 1H) 455 500 MHz 7.47 (d, J = 1.82Hz, 1H), 7.35 (d, J = 8.30 Hz, 1H), — — DMSO - 7.22 (dd, J = 1.75, 8.37Hz, 1H), 4.75 (s, 2H), 4.24- d₆ 4.31 (m, 2H), 3.95 (t, J = 7.66 Hz, 2H),3.33-3.38 (m, 1H), 2.97-3.06 (m, 2H), 2.80 (dd, J = 8.30, 12.59 Hz, 1H),2.36 (s, 1H), 2.29 (quin, J = 7.62 Hz, 2H), 2.08-2.17 (m, 1H), 1.74-1.94(m, 1H) 456 600 MHz 8.91 (s, 2H), 7.22 (dd, J = 2.41, 9.81 Hz, 1H), 7.14— — DMSO - (dd, J = 4.79, 8.68 Hz, 1H), 6.85 (ddd, J = 2.49, 8.70, d₆9.91 Hz, 1H), 5.49 (d, J = 2.10 Hz, 2H), 3.36-3.43 (m, 2H), 3.28-3.30(m, 3H), 2.90-2.99 (m, 1H), 2.66-2.72 (m, 2H), 1.98-2.06 (m, 1H), 1.62(br s, 1H), 1.33-1.42 (m, 1H) 457 600 MHz 7.38-7.43 (m, 1H), 7.12 (dd, J= 2.49, 9.26 Hz, 1H), B Chiralpak DMSO - 6.90-6.96 (m, 1H), 5.07-5.16(m, 2H), 4.23-4.50 AD-H, 25% d₆ (m, 1H), 4.23 (q, J = 9.45 Hz, 1H),3.21-3.29 (m, IPA, peak 1 3H), 2.93-3.01 (m, 3H), 2.72-2.81 (m, 1H),1.96- 2.12 (m, 1H), 1.72-1.90 (m, 3H) 458 600 MHz 8.93 (dd, J = 0.66,2.06 Hz, 1H), 8.34 (dd, J = 2.14, B Chiralpak DMSO - 8.21 Hz, 1H), 7.72(d, J = 8.10 Hz, 1H), 7.61 (d, AD-H, 25% d₆ J = 8.56 Hz, 1H), 7.49 (d, J= 8.10 Hz, 1H), 5.66 (d, IPA, peak 1 J = 1.71 Hz, 2H), 4.32-4.43 (m,1H), 3.50-3.64 (m, 2H), 3.15-3.28 (m, 1H), 2.85-2.94 (m, 2H), 2.04- 2.12(m, 1H), 1.66-1.77 (m, 1H) 459 600 MHz 7.66 (s, 1H), 7.57 (d, J = 8.25Hz, 1H), 7.41 (dd, B Chiralpak DMSO - J = 1.25, 8.33 Hz, 1H), 5.11-5.21(m, 2H), AD-H, 25% d₆ 4.38-4.49 (m, 1H), 3.64-3.72 (m, 2H), 3.61 (td,IPA, peak 1 J = 4.74, 9.75 Hz, 4H), 3.44-3.53 (m, 2H), 3.34- 3.41 (m,1H), 3.17 (d, J = 4.90 Hz, 1H), 3.09 (ddd, J = 2.84, 9.48, 12.59 Hz,1H), 2.95-3.05 (m, 1H), 2.86 (dd, J = 8.06, 12.65 Hz, 1H), 2.09-2.19 (m,1H), 1.75-1.93 (m, 1H) 460 600 MHz 7.23 (d, J = 9.81 Hz, 1H), 7.16-7.20(m, 1H), 6.92 B Chiralpak DMSO - (t, J = 8.84 Hz, 1H), 5.08-5.17 (m,2H), 4.32-4.51 AD-H, 25% d₆ (m, 1H), 4.23 (q, J = 9.55 Hz, 2H),3.34-3.39 (m, IPA, peak 2 1H), 3.25-3.30 (m, 4H), 2.93-3.05 (m, 2H),2.74- 2.85 (m, 1H), 2.03-2.13 (m, 1H), 1.71-1.89 (m, 1H) 461 600 MHz7.39 (d, J = 8.41 Hz, 1H), 7.33 (d, J = 2.02 Hz, 1H), B Chiralpak DMSO -7.09 (dd, J = 2.10, 8.41 Hz, 1H), 4.94-5.05 (m, 2H), AD-H, 25% d₆4.70-4.84 (m, 1H), 3.14-3.28 (m, 2H), 3.10-3.13 IPA, peak 1 (m, 6H),2.91-3.06 (m, 2H), 2.89 (s, 1H), 1.87- 2.05 (m, 1H), 1.68 (br s, 1H) 462600 MHz 8.42 (br s, 2H), 7.44-7.48 (m, 1H), 7.20 (dd, B Chiralpak DMSO -J = 2.37, 9.23 Hz, 1H), 6.99 (t, J = 9.27 Hz, 1H), AD-H, 25% d₆5.10-5.21 (m, 2H), 5.04-5.10 (m, 1H), 4.36-4.55 IPA, peak 1 (m, 1H),4.23 (q, J = 9.52 Hz, 2H), 3.78 (br s, 1H), 3.48 (br dd, J = 4.01, 12.42Hz, 1H), 3.26-3.34 (m, 1H), 3.02-3.17 (m, 2H), 2.99 (s, 1H), 2.51-2.65(m, 1H), 1.95-2.12 (m, 2H) 463 600 MHz 8.95 (d, J = 1.32 Hz, 1H), 8.30(dd, J = 2.10, 8.17 — — DMSO - Hz, 1H), 7.38-7.45 (m, 2H), 7.07 (dd, J =2.49, 9.19 d₆ Hz, 1H), 6.92 (ddd, J = 2.57, 8.66, 10.10 Hz, 1H),5.47-5.57 (m, 2H), 3.24-3.31 (m, 3H), 3.13-3.23 (m, 2H), 2.99-3.10 (m,2H), 2.89-2.98 (m, 2H), 1.75-1.89 (m, 1H), 1.53-1.67 (m, 1H). 464 600MHz 8.44 (br s, 2H), 7.74 (s, 1H), 7.62 (d, J = 8.33 Hz, B ChiralpakDMSO - 1H), 7.46 (d, J = 8.21 Hz, 1H), 5.14-5.24 (m, 2H), AD-H, 25% d₆4.88 (dt, J = 4.87, 9.32 Hz, 1H), 4.69-4.83 (m, 1H), IPA, peak 14.42-4.55 (m, 1H), 3.73-3.83 (m, 1H), 3.69 (br d, J = 4.36 Hz, 3H),3.57-3.65 (m, 4H), 3.37-3.56 (m, 3H), 2.99-3.17 (m, 2H), 2.24 (br t, J =9.46 Hz, 1H), 1.83-1.92 (m, 1H) 465 600 MHz 8.73 (br s, 2H), 7.46-7.50(m, 1H), 7.21-7.23 (m, B Chiralpak DMSO - 1H), 6.98-7.02 (m, 1H),5.17-5.22 (m, 1H), 4.36- AD-H, 25% d₆ 4.53 (m, 1H), 4.13-4.32 (m, 2H),3.95-4.13 (m, IPA, peak 1 2H), 3.64 (br d, J = 12.53 Hz, 1H), 3.25-3.34(m, 3H), 3.09-3.15 (m, 1H), 2.52-2.65 (m, 3H) 466 600 MHz 8.38 (br s,2H), 7.23-7.30 (m, 1H), 6.99 (t, J = 9.27 B Chiralpak DMSO - Hz, 1H),5.05-5.21 (m, 2H), 4.49 (q, J = 8.93 Hz, AD-H, 25% d₆ 1H), 4.23 (q, J =9.52 Hz, 2H), 3.79 (br s, 1H), IPA, peak 1 3.44-3.66 (m, 1H), 3.30-3.37(m, 1H), 3.28 (s, 2H), 3.06-3.18 (m, 1H), 2.52-2.55 (m, 3H), 1.93- 2.11(m, 1H) 467 600 MHz 8.91 (s, 2H), 7.40 (dd, J = 4.87, 8.68 Hz, 1H), 7.07B Chiralpak DMSO - (dd, J = 2.53, 9.30 Hz, 1H), 6.91 (ddd, J = 2.53,8.62, AD-H, 25% d₆ 10.10 Hz, 1H), 5.46-5.57 (m, 2H), 3.25-3.31 (m, IPA,peak 1 3H), 3.12-3.22 (m, 1H), 2.90-3.08 (m, 4H), 1.84 (dtd, J = 3.58,7.67, 13.31 Hz, 1H), 1.49-1.64 (m, 1H), 1.40 (br s, 1H) 468 600 MHz 7.47(d, J = 8.56 Hz, 1H), 7.31 (s, 1H), 7.06 (dd, B SFC: DMSO - J = 1.21,8.60 Hz, 1H), 4.97-5.07 (m, 2H), Chiralpak d⁶ 4.34-4.45 (m, 1H), 3.32(s, 1H), 3.12 (s, 3H), 2.95- AD-H 3.09 (m, 2H), 2.89 (s, 3H), 2.76-2.85(m, 1H), analytical 2.06-2.15 (m, 1H), 1.72-1.89 (m, 2H) column, 15%methanol with 0.2% DEA 469 600 MHz 9.07 (br s, 2H), 7.44-7.48 (m, 1H),7.21 (dd, — — DMSO - J = 2.57, 9.26 Hz, 1H), 6.96-7.03 (m, 1H), 5.06- d₆5.19 (m, 2H), 4.92-5.03 (m, 1H), 4.23 (q, J = 9.58 Hz, 2H), 3.56-3.86(m, 2H), 3.46 (br s, 1H), 3.29 (s, 3H), 3.11 (br dd, J = 9.89, 12.61 Hz,1H), 2.92- 3.04 (m, 1H), 2.68 (br s, 3H), 2.16-2.25 (m, 1H), 1.82-1.95(m, 1H) 470 600 MHz 7.58 (d, J = 1.82 Hz, 1H), 7.17-7.24 (m, 2H), 4.70-B SFC: DMSO - 4.77 (m, 2H), 4.46-4.35 (m, 1H), 4.21-4.29 (m, ChiralpakIC, d₆ 2H), 3.94 (t, J = 7.72 Hz, 2H), 3.33-3.41 (m, 2H), 45% 2.97-3.08(m, 2H), 2.82 (dd, J = 8.30, 12.59 Hz, methanol 1H), 2.28 (quin, J =7.72 Hz, 2H), 2.14 (ddd, Peak 2 J = 4.61, 8.66, 17.09 Hz, 1H), 1.73-1.88(m, 1H) 471 600 MHz 7.44 (d, J = 2.02 Hz, 1H), 7.19 (d, J = 8.49 Hz,1H), B SFC: DMSO - 7.07 (dd, J = 2.02, 8.41 Hz, 1H), 4.93-5.04 (m, 2H),Chiralpak IC, d₆ 4.79-4.84 (m, 1H), 4.70-4.76 (m, 1H), 3.10-3.23 30% (m,6H), 2.94-3.10 (m, 2H), 2.88 (s, 2H), 1.86- methanol 2.05 (m, 1H), 1.75(br s, 1H) Peak 2 472 600 MHz 7.21 (d, J = 9.28 Hz, 1H), 6.96-7.03 (m,2H), 5.09- — — DMSO - 5.17 (m, 2H), 4.17-4.40 (m, 1H), 3.39-3.56 (m, d₆1H), 3.13-3.25 (m, 2H), 3.00 (s, 1H), 2.89 (br t, J = 10.63 Hz, 1H),2.52-2.55 (m, 2H), 2.35-2.46 (m, 2H), 1.92-2.00 (m, 2H), 1.73-1.86 (m,1H), 1.19- 1.29 (m, 1H), 473 600 MHz 7.74 (s, 1H), 7.37-7.46 (m, 2H),5.08-5.18 (m, B SFC: IC, 15% DMSO - 2H), 4.36-4.50 (m, 1H), 3.56-3.72(m, 6H), 3.42- methanol d₆ 3.54 (m, 2H), 3.35-3.41 (m, 2H), 2.98-3.11(m, Peak 2 2H), 2.85 (dd, J = 8.17, 12.61 Hz, 1H), 2.03-2.19 (m, 1H),1.75-1.91 (m, 1H) 474 600 MHz 7.39 (s, 1H), 7.26 (d, J = 8.56 Hz, 1H),7.05 (d, B SFC: DMSO - J = 8.79 Hz, 1H), 4.98-5.11 (m, 2H), 3.35-3.41(m, Chiralpak d₆ 1H), 3.11-3.17 (m, 3H), 2.96-3.10 (m, 2H), 2.89 AD-H(s, 3H), 2.77-2.86 (m, 1H), 2.07-2.17 (m, 1H), analytical 1.73-1.90 (m,3H) column, 15% methanol with 0.2% DEA. Peak 2 475 600 MHz 7.40 (s, 1H),7.29 (d, J = 8.64 Hz, 1H), 7.06 (d, B Chiralcel OD- DMSO - J = 8.63 Hz,1H), 4.98-5.12 (m, 2H), 4.37-4.48 (m, H column d₆ 1H), 3.56-3.71 (m,5H), 3.41-3.54 (m, 2H), 3.37- Peak 2 3.41 (m, 1H), 3.12-3.26 (m, 2H),2.93-3.09 (m, 2H), 2.79-2.90 (m, 1H), 2.05-2.22 (m, 1H), 1.75- 1.87 (m,1H) 476 600 MHz 8.90 (s, 1H), 8.27 (dd, J = 2.10, 8.25 Hz, 1H), 7.30 BSFC: DMSO - (d, J = 8.33 Hz, 1H), 6.87 (dd, J = 2.18, 9.34 Hz, Chiralpakd₆ 1H), 6.57 (dd, J = 2.18, 11.91 Hz, 1H), 5.48-5.56 AD-H, 25% (m, 2H),4.37 4.45(m, 1H), 3.55 (s, 3H), 3.38-3.48 methanol (m, 2H), 3.17 (s,1H), 2.96-3.06 (m, 2H), 2.81 (dd, Peak1 J = 8.91, 12.57 Hz, 1H),2.01-2.11 (m, 1H), 1.68- 1.80 (m, 1H) 477 600 MHz 8.91 (s, 2H), 7.22(dd, J = 2.49, 9.81 Hz, 1H), 7.10 B SFC: DMSO - (dd, J = 4.75, 8.72 Hz,1H), 6.84 (ddd, J = 2.49, 8.70, Phenomenex d₆ 9.91 Hz, 1H), 5.46-5.58(m, 2H), 3.26-3.31 (m, Lux 3H), 2.98-3.24 (m, 4H), 2.93 (td, J = 3.28,6.75 Hz, Cellulose-2, 1H), 1.86 (dtd, J = 3.54, 7.61, 13.38 Hz, 1H),1.58- 15% 1.66 (m, 1H), 1.40 (br s, 1H) methanol. Peak2 478 600 MHz 8.47(br s, 2H), 7.78 (s, 1H), 7.44-7.50 (m, 2H), B SFC: DMSO - 5.09-5.23 (m,2H), 4.80-4.88 (m, 1H), 3.72-3.84 Chiralpak IC, d₆ (m, 1H), 3.69 (br d,J = 4.52 Hz, 3H), 3.57-3.66 (m, 15% 4H), 3.38-3.53 (m, 2H), 3.13 (br dd,J = 10.32, methanol. 12.57 Hz, 1H), 3.05 (br t, J = 11.60 Hz, 1H), 2.24Peak2 (br t, J = 9.54 Hz, 1H), 1.85-1.93 (m, 1H), 1.15-1.27 (m, 1H) 479600 MHz 7.26-7.29 (m, 1H), 7.25 (t, J = 6.83 Hz, 1H), 6.99 (t, B FCusing an DMSO - J = 9.32 Hz, 1H), 5.05-5.21 (m, 2H), 4.87-5.01 (m, (2 ×Chiralpak d₆ 1H), 4.23 (q, J = 9.55 Hz, 2H), 3.69-3.79 (m, 1H), IC 2 ×25 cm, 5 3.58 (dt, J = 4.36, 8.99 Hz, 1H), 3.27-3.30 (m, 3H), μmcolumn), 3.06-3.14 (m, 1H), 2.97-3.03 (m, 2H), 2.65 (s, Peak2 3H),2.16-2.25 (m, 1H), 1.81-1.95 (m, 1H) 480 600 MHz 8.23-8.31 (br s, 1H),6.90-7.33 (m, 3H), 5.13-5.26 — — DMSO - (m, 2H), 4.11-4.29 (m, 1H),3.82-3.91 (m, 1H), d₆ 3.63 (br d, J = 9.19 Hz, 1H), 3.45-3.59 (m, 1H),3.36 (td, J = 8.29, 16.43 Hz, 1H), 3.28 (s, 3H), 3.10- 3.23 (m, 1H),2.52-2.55 (m, 1H), 2.34-2.47 (m, 1H), 0.97-1.19 (m, 3H) 481 600 MHz7.28-7.59 (m, 1H), 7.05-7.16 (m, 1H), 6.75-6.95 — — DMSO - (m, 1H),4.77-4.93 (m, 1H), 4.08-4.53 (m, 1H), d₆ 4.02-4.32 (m, 1H), 3.32-3.32(m, 2H), 3.21-3.30 (m, 1H), 2.76-2.93 (m, 1H), 2.53-2.70 (m, 1H),1.68-1.86 (m, 1H), 1.45-1.63 (m, 1H), 1.02-1.18 (m, 1H), −0.05-0.15 (m,1H) 482 600 MHz 8.70 (br s, 2H), 7.26-7.32 (m, 1H), 7.02 (ddd, B SFCwith DMSO - J = 2.53, 8.86, 9.79 Hz, 1H), 5.15-5.24 (m, 1H), ChiralcelOD- d₆ 4.12-4.30 (m, 2H), 4.03-4.12 (m, 1H), 3.68 (br d, H, 10% J =11.91 Hz, 5H), 3.26-3.40 (m, 3H), 3.11-3.18 (m, methanol 1H), 2.65 (brs, 1H), 2.58-2.63 (m, 1H), 2.52-2.56 Peak2 (m, 4H) 483 600 MHz 8.70 (brs, 2H), 7.26-7.32 (m, 2H), 7.02 (ddd, B SFC: DMSO - J = 2.53, 8.86, 9.79Hz, 1H), 5.15-5.24 (m, 2H), Chiralpak IC, d₆ 4.12-4.30 (m, 2H),4.03-4.12 (m, 2H), 3.68 (br d, 25% J = 11.91 Hz, 2H), 3.26-3.40 (m, 4H),3.11-3.18 (m, isopropanol. 1H), 2.65 (br s, 1H), 2.58-2.63 (m, 1H).Peak2 484 600 MHz 8.14 (br s, 2H), 7.22-7.27 (m, 2H), 7.11-7.19 (m, BSFC: DMSO - 1H), 5.03-5.15 (m, 2H), 4.23 (dq, J = 3.35, 9.37 Hz,Chiralpak IC, d₆ 1H), 3.58-3.69 (m, 2H), 3.27 (s, 3H), 3.15-3.25 25% (m,2H), 2.96-3.03 (m, 2H), 2.85-2.93 (m, 1H), isopropanol. 1.79-2.00 (m,1H), 1.55-1.61 (m, 1H) Peak1 485 600 MHz 8.14 (br s, 2H), 7.23-7.28 (m,2H), 6.98 (t, J = 9.21 B SFC using an DMSO - Hz, 1H), 5.03-5.18 (m, 2H),4.23 (q, J = 9.47 Hz, Chiralpak IC d₆ 2H), 3.63-3.82 (m, 1H), 3.47 (brs, 1H), 3.29-3.42 2 × 25 cm, 5 (m, 1H), 3.28 (s, 2H), 2.97-3.11 (m, 2H),2.87- micron, a 2.96 (m, 1H), 2.52-2.55 (m, 4H), 2.14-2.31 (m, mobilephase 1H), 1.38-1.50 (m, 1H) of 25% isopropanol Peak 2 486 600 MHz 8.23(br s, 2H), 7.15-7.28 (m, 1H), 6.98-7.14 (m, B SFC: DMSO - 2H),6.78-6.91 (m, 1H), 5.09-5.28 (m, 1H), 4.16- Chiralpak d₆ 4.29 (m, 1H),3.50-3.89 (m, 3H), 3.40-3.49 (m, AD-H 1H), 3.26-3.30 (m, 2H), 2.54 (s,2H), 2.15-2.33 analytical (m, 1H) column, 25% isopropano Peak1 487 600MHz 8.23 (br s, 2H), 7.14-7.28 (m, 1H), 7.12 (br s, 1H), B SFC: DMSO -6.99-7.10 (m, 1H), 5.16-5.29 (m, 1H), 4.16-4.29 Chiralpak d₆ (m, 1H),3.64-3.83 (m, 2H), 3.41 (br s, 2H), 3.37- AD-H 3.39 (m, 1H), 3.26-3.29(m, 2H), 2.52-2.55 (m, analytical 2H), 2.15-2.33 (m, 1H) column, 25%isopropano Peak2 488 600 MHz 7.36-7.43 (m, 1H), 7.09 (dd, J = 2.49, 9.34Hz, 1H), B SFC using DMSO - 6.87-6.96 (m, 1H), 5.03-5.09 (m, 2H), twoRegis d₆ 4.17-4.28 (m, 2H), 3.73-3.79 (m, 1H), 3.71 (br d, Whelk-O s, sJ = 3.11 Hz, 1H), 3.40-3.49 (m, 2H), 3.23-3.29 (m, 2 × 25 cm, 5 1H),2.89-3.08 (m, 6H), 2.51-2.57 (m, 1H), 1.72- micron 1.82 (m, 1H) columnsPeak2 489 600 MHz 7.16-7.21 (m, 1H), 7.05 (dd, J = 2.49, 9.42 Hz, 1H), —— DMSO - 6.78-6.84 (m, 1H), 5.07-5.19 (m, 2H), d₆ 4.20-4.46 (m, 2H),3.52-3.65 (m, 2H), 3.40-3.51 (m, 2H), 3.26 (s, 3H), 3.07-3.14 (m, 1H),1.87- 2.00 (m, 1H), 1.62 (qd, J = 6.18, 12.45 Hz, 1H) 490 600 MHz7.16-7.21 (m, 1H), 7.05 (dd, J = 2.49, 9.42 Hz, 1H), — — DMSO -6.78-6.84 (m, 1H), 5.07-5.19 (m, 2H), d₆ 4.16-4.31 (m, 2H), 3.92 (br s,1H), 3.77 (br s, 1H), 3.44-3.58 (m, 3H), 3.25-3.29 (m, 1H), 2.99 (s,1H), 2.52-2.55 (m, 1H), 2.28 (qd, J = 7.20, 13.97 Hz, 1H), 2.00 (br d, J= 4.83 Hz, 1H) 491 600 MHz 7.17-7.23 (m, 1H), 7.08 (dd, J = 2.49, 9.42Hz, 1H), — — DMSO - 6.79-6.89 (m, 1H), 5.07-5.21 (m, 2H), 4.16- d₆4.41(m, 2H), 3.39-3.58 (m, 2H), 3.14-3.27 (m, 2H), 2.94-3.03 (m, 1H),2.68 (br d, J = 6.93 Hz, 2H), 2.52-2.57 (m, 1H), 2.27-2.34 (m, 1H),1.95- 2.04 (m, 1H), 1.65 (qd, J = 8.03, 12.28 Hz, 1H) 492 600 MHz 1.79(br dd, J = 8.64, 3.11 Hz, 1H) 1.84 (br s, 1H) — — DMSO - 2.88-2.97 (m,2H) 2.97-3.13 (m, 4H) 3.17 (s, d₆ 1H), 3.24-3.28 (m, 3H) 3.38-3.53 (m,2H) 3.68- 3.80 (m, 2H) 4.17-4.28 (m, 2H) 4.48 (q, J = 8.93 Hz, 1H) 5.00(s, 1H) 5.07 (s, 1H) 6.87-6.94 (m, 1H) 7.15 (dd, J = 8.68, 4.79 Hz, 1H)7.18-7.25 (m, 1H) 493 600 MHz 1.65-1.82 (m, 2H) 1.84 (br s, 1H)2.52-2.56 (m, — — DMSO - 1H) 2.90-2.96 (m, 2H) 2.98-3.13 (m, 5H) 3.17 d₆(s, 1H) 3.24-3.28 (m, 3H) 3.38-3.53 (m, 3H) 3.69-3.79 (m, 2H) 4.09 (brs, 1H) 4.16-4.29 (m, 2H) 4.48 (q, J = 9.16 Hz, 1H) 5.00 (s, 1H) 5.07 (s,2H) 6.88-6.94 (m, 1H) 7.13-7.25 (m, 2H)

Intermediate 60: tert-butyl((3R,4R)-1-(6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate

Step 1. 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile

To a solution of 1,2-diamino-4-cyanobenzene (1.00 mL, 7.51 mmol) intetrahydrofuran (5 mL) was added 1,1′-carbonyldiimidazole (1.22 g, 7.51mmol). The reaction was stirred at ambient temperature for one hour,concentrated, then triturated with water. The brown precipitate wascollected by vacuum filtration to provide2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile as a brown powder.MS (ESI, pos. ion) m/z: 160.2 [M+1]

Step 2. 2-chloro-1H-benzo[d]imidazole-6-carbonitrile

To a suspension of 2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carbonitrile(XVIII, 1.19 g, 7.48 mmol. 1 equiv) in acetonitrile (5 mL) was addedphosphorus(v) oxychloride (1.398 mL, 14.95 mmol). The reaction wasstirred at 110° C. for 16 hours, then cooled to room temperature. It wasdiluted with acetonitrile and then slowly added to a cold,rapidly-stirring beaker of saturated aqueous sodium bicarbonate (50 mL).The mixture was extracted with ethyl acetate, which was dried overanhydrous magnesium sulfate, filtered, and concentrated to provide2-chloro-1H-benzo[d]imidazole-6-carbonitrile as a tan powder. (ESI, pos.ion) m/z: 178.2 [M+1]

Step 3, tert-butyl((3R,4R)-1-(6-cyano-H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(Intermediate 60)

N,N-diisopropylethylamine (3.93 mL, 22.52 mmol),2-chloro-1H-benzo[d]imidazole-6-carbonitrile (2 g. 11.26 mmol),tert-butyl ((3R,4R)-4-fluoropiperidin-3-yl)carbamate (2.95 g, 13.51mmol), and 1-butanol (25 mL) were combined in a flask and heated to 130C for 48 hours. The mixture was concentrated, then loaded onto a 125 gRediSep ISCO cartridge, eluting with 0-4% MeOH in DCM to provide thetitle compound as a light brown foam. (ESI, pos. ion) m % z: 360.2 [M+1]

The blowing intermediates were synthesized using a sequence analogous tothat described for intermediate 60 and general scheme 9 above:

TABLE 4 SnAr Intermediates prepared following Scheme 9 Int # StructureCompound Name MS MH+ 60

tert-butyl ((3R,4R)-1-(6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3- yl)carbamate 360.2 61

(S)-tert-butyl (1-(1H-benzo[d]imidazol-2-yl)piperidin-3-yl)(methyl)carbamate 331.3 62

tert-butyl ((3R,4R)-1-(4,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3- yl)carbamate 371.2 63

tert-butyl 6-(4,6-difluoro-1H- benzo[d]imidazol-2-yl)hexahydro-2H-pyrido[4,3-b][1,4]oxazine-4(3H)- carboxylate 396.2 64

tert-butyl ((3R,4R)-1-(6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3- yl)(methyl)carbamate 374.265

tert-butyl ((3R,4R)-4-fluoro-1-(6-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-3- yl)carbamate 353.2 66

(R)-tert-butyl (1-(6-chloro-1H- benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-yl)carbamate 387.2 67

tert-butyl ((3R,4R)-1-(1H- benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate 335.0 68

tert-butyl ((3R,4R)-1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3- yl)carbamate 371.2 69

tert-butyl ((3R,4R)-1-(6-chloro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3- yl)carbamate 369.2 70

(R)-tert-butyl (1-(4,6-difluoro-1H- benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-yl)carbamate 389.2 71

(S)-tert-butyl (1-(1H-benzo[d]imidazol-2- yl)piperidin-3-yl)carbamate317.2 72

(R)-tert-butyl (1-(1H-benzo[d]imidazol-2- yl)piperidin-3-yl)carbamate317.2 73

(R)-tert-butyl (1-(1H-benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-yl)carbamate 353.2 74

tert-butyl ((3R,4S)-1-(6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3- yl)carbamate 360.2 75

tert-butyl ((3R,4R)-1-(6-fluoro-1H-benzo[d]imidazol-2-yl)-4-hydroxypiperidin- 3-yl)carbamate 351.2 76

tert-butyl ((3R,4S)-1-(5,6-diffuoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3- yl)carbamate 371.0 77

tert-butyl ((3R,4S)-4-fluoro-1-(6-(trifluoromethyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-yl)carbamate403.2 78

(R)-tert-butyl (1-(5,6-diffuoro-1H- benzo[d]imidazol-2-yl)-4,4-difluoropiperidin-3-yl)carbamate 389.2 79

tert-butyl ((3R,4S)-1-(1H- benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate 335.2 80

tert-butyl ((3R,4S)-1-(6-fluoro-1H-benzo[d]imidazol-2-yl)-4-hydroxypiperidin- 3-yl)carbamate 351.2 81

tert-butyl ((3R,4R)-4-fluoro-1-(6- (trifluoromethyl)-1H-imidazo[4,5-b]pyridin-2-yl)piperidin-3-yl)carbamate 404.2 82

tert-butyl ((3R,4R)-4-fluoro-1-(6-fluoro-4-methoxy-1H-benzo[d]imidazol-2- yl)piperidin-3-yl)carbamate 383.2 83

tert-butyl ((3R,4R)-4-fluoro-1-(6-(trifluoromethyl)-1H-benzo[d]imidazo-2- yl)piperidin-3-yl)carbamate403.2 84

tert-butyl ((3R,4R)-4-fluoro-1-(6-fluoro-1H-imidazo[4,5-b]pyridin-2-yl)piperidin-3- yl)carbamate 354.2 85

(R)-tert-butyl (4,4-difluoro-1-(6-fluoro-1H-benzo[d]imidazol-2-yl)piperidin-3- yl)carbamate 371.2

Example 187:2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Step 1. tert-butyl((3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate

Cesium carbonate (0.707 mg, 2.170 mmol), tert-butyl((3R,4R)-1-(6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(390 mg, 1.085 mmol). (5-chloropyrimidin-2-yl)methyl methanesulfonate(290 mg, 1.302 mmol), and acetonitrile (10 mL) were combined in a vialand stirred overnight. The mixture was poured into water and extractedwith DCM (3×). The organics were combined, dried over Na2SO4, filtered,and concentrated. The brown solid was dissolved in DCM, loaded onto a 20g plug of silica and flushed with EtOAc (˜4 column volumes). The EtOAcwas concentrated to provide tert-butyl((3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamateand tert-butyl((3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-5-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamateas a mixture of isomers. The isomers were separated using chiral SFC(Chiralcel AD, 25% IPA, peak 1). (ESI, pos. ion) m/z: 486.2 [M+1]

Boc Deprotection using TFA (Procedure B)

Step 2.2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile(Example 187)

tert-Butyl((3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-cyano-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(150 mg, 0.309 mmol) was loaded into a vial. DCM (5 mL), then TFA (2 mL)was added. After 1 hour, the mixture was poured onto an SCX column,prewetted with methanol, flushed with methanol, then eluted withmethanolic ammonia. The residue was redissolved in MeCN/H₂0, frozen, andlyophilized to provide the title compound as a white solid. ¹H NMR (500MHz, MeOD) δ 8.80 (s, 2H), 7.65-7.69 (m, 1H), 7.54-7.61 (m, 1H). 7.49(d, J=8.30 Hz, 1H), 5.57 (s, 2H). 4.42-4.60 (m, 1H). 3.72-3.80 (m, 1H).3.64 (br d. J=13.23 Hz, 1H), 3.15-3.27 (m, 2H), 3.06 (dd, J=9.21, 12.59Hz, 1H), 2.13-2.27 (m, 1H), 1.80-1.99 (m, 1H). (ESI, pos. ion) m/z:386.2 [M+1]

Note: In some cases, the free base was redissolved in DCM, and HC wasadded to crash out the HC salt. This is noted in the table as a TFAdeprotection, but HCl product.

Alternative Boc Deprotection with HCl (Procedure A)

Step 2.2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-methoxypyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrilehydrochloride (Example 242)

tert-Butyl((3R,4R)-1-(6-cyano-1-((5-methoxypyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(69 mg) was dissolved in dioxane (2 mL), and 4 N HCl in dioxane (500 uL)was added. The reaction was stirred at ambient temperature overnight,then concentrated in vacuo to provide the title compound as a whitesolid. ¹H NMR (500 MHz, MeOD) δ 8.52 (s, 2H). 7.94 (s, 1H), 7.66-7.74(m, 2H). 5.54-5.67 (m, 2H). 4.77-4.93 (m, 1H). 4.21-4.30 (m, 1H), 4.01(br d, J=12.98 Hz, 1H), 3.96 (s, 3H), 3.71-3.78 (m, 1H), 3.43-3.50 (m,2H), 2.32-2.46 (m, 1H), 1.98-2.14 (m, 1H). (ESI, pos. ion) mz: 382.2[M+1].

Note: HCl salt was sometimes free based using an aqueous work up orusing ion exchange chromatography. Isolation of salt or free base isspecified in table.

The following compounds were made in a manner analogous to that outlinedin Schemes 9 and 10:

Example 188

(3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine(3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-aminewas synthesized on 0.3 mmol scale following a sequence analogous to thatdescribed above. The Boc deprotection was accomplished using the TFAprocedure. ¹H NMR (500 MHz, MeOD) δ 8.68-8.74 (s, 2H), 7.47-7.52 (m,1H), 7.14-7.20 (m, 2H), 7.08-7.13 (m, 1H), 5.53 (s, 2H), 4.34-4.52 (m,1H), 3.64 (dtd, J=1.95, 4.14, 12.36 Hz, 1H), 3.48-3.57 (m, 1H),3.04-3.21 (m, 2H), 2.98 (dd, J=8.82, 12.20 Hz, 1H), 2.12-2.25 (m, 1H),1.82-1.92 (m, 1H). (ESI, pos. ion) m/z: 345.2 [M+1].

The following Examples were synthesized using a sequence analogous tothat described for examples 239-240 and general scheme 9-10 above:

TABLE 5 Compounds made following schemes 9-10 Boc Depro- SnAr tectionEx. Inter- Pro- MS # mediate Electrophile cedure Structure Compound NameMH+ 187 60

B

(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 386.0 188 67

B

(3R,4R)-4-fluoro-1-(1- ((5-fluoropyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 345.2 189 67

B

(3R,4R)-4-fluoro-1-(1- ((5-fluoropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 344.2 190 60

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-fluoropyridin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 369.0 191 60

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-fluoropyridin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 369.2 192 67

B

(3R,4R)-1-(1-((5- bromopyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 405.0 193 67

B

(3R,4R)-4-fluoro-1-(1- ((5- (trifluoromethyl)pyrimidin- 2-yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 395.2 194 67

B

(3R,4R)-4-fluoro-1-(1- ((5-methoxypyrimidin- 2-yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 357.2 195 67

B

(3R,4R)-1-(1-((5- chloropyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 361.8 196 60

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-fluoropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 370.0 197 60

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-fluoropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 370.0 198 60

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-cyanopyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 386.0 199 73

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 370.0 200 60

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-bromopyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 432.0 201 60

B

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-bromopyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 432.0 202 67

B

5-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)pyrazine-2- carbonitrile 352.2 203 74

B

2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile 386.2 204 74

B

2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile 386.2 205 75

B

(3R,4R)-3-amino-1-(1- ((5-chloropyrimidin-2- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2- yl)piperidin-4-ol 377.0 206 75

B

(3R,4R)-3-amino-1-(1- ((5-chloropyrimidin-2- yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2- yl)piperidin-4-ol 377.0 207 75

B

6-((2-((3R,4R)-3- amino-4- hydroxypiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 367.2 208 75

B

6-((2-((3R,4R)-3- amino-4- hydroxypiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 367.2 209 71

B

(S)-1-(1-((5- chloropyridin-2- yl)methyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 342.0 210 71

B

(S)-5-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)picolinonitrile 333.2 211 67

A

(3R,4R)-1-(1-((5- chloropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 360.0212 73

A

(R)-6-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile hydrochloride 369.0 213 60

B^(a)

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyridin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile hydrochloride 385.0 21460

B^(a)

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-chloropyridin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile hydrochloride 385.0 21567

B^(a)

(3R,4R)-1-(1-((R)-1-(5- chloropyridin-2- yl)ethyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 374.2216 67

B^(a)

(3R,4R)-1-(1-((S)-1-(5- chloropyridin-2- yl)ethyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 374.2217 68

B^(a)

(3R,4R)-1-(1-((R)-1-(5- chloropyridin-2- yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2- yl)-4-fluoropiperidin-3- amine hydrochloride410.2 218 68

B^(a)

(3R,4R)-1-(1-((S)-1-(5- chloropyridin-2- yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2- yl)-4-fluoropiperidin-3- amine hydrochloride410.2 219 69

B^(a)

(3R,4R)-1-(5-chloro-1- ((R)-1-(5-chloropyridin- 2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 408.0220 69

B^(a)

(3R,4R)-1-(5-chloro-1- ((S)-1-(5-chloropyridin- 2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 408.0221 69

B^(a)

(3R,4R)-1-(6-chloro-1- ((R)-1-(5-chloropyridin- 2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 408.0   222 a 69

B^(a)

(3R,4R)-1-(6-chloro-1- ((S)-1-(5-chloropyridin- 2-yl)ethyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 408.0223 60

B^(a)

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((R)-1-(5-cyanopyridin-2-yl)ethyl)-1H- benzo[d]imidazole-6- carbonitrile hydrochloride 390.2224 60

B^(a)

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((R)-1-(5-cyanopyridin-2-yl)ethyl)-1H- benzo[d]imidazole-5- carbonitrile hydrochloride 390.2225 60

B^(a)

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((S)-1-(5-cyanopyridin-2-yl)ethyl)-1H- benzo[d]imidazole-6- carbonitrile hydrochloride 390.2226 60

B^(a)

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((S)-1-(5-cyanopyridin-2-yl)ethyl)-1H- benzo[d]imidazole-5- carbonitrile hydrochloride 390.2227 68

B^(a)

(3R,4R)-1-(1-((5- chloropyridin-2- yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2- yl)-4-fluoropiperidin-3- amine hydrochloride396.2 228 68

B^(a)

(3R,4R)-1-(5,6- difluoro-1-((5- fluoropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine hydrochloride 380.2229 70

B^(a)

(R)-1-(1-((5- chloropyridin-2- yl)methyl)-5,7-difluoro-1H-benzo[d]imidazol-2- yl)-4,4- difluoropiperidin-3- amine hydrochloride414.2 230 70

B^(a)

(R)-1-(1-((5- chloropyridin-2- yl)methyl)-4,6-difluoro-1H-benzo[d]imidazol-2- yl)-4,4- difluoropiperidin-3- amine hydrochloride414.2 231 67

A

(R)-1-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)-2,3-dihydro-1H- indene-5-carbonitrilehydrochloride 376.2 232 67

A

(S)-1-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)-2,3-dihydro-1H- indene-5-carbonitrilehydrochloride 376.2 233 66

A

(R)-5-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1- yl)methyl)pyrazine-2- carbonitrile 404.0 234 66

A

(R)-5-((2-(3-amino-4,4- difluoropiperidin-1-yl)- 5-chloro-1H-benzo[d]imidazol-1- yl)methyl)pyrazine-2- carbonitrile 404.0 235 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-isopropylacetamide 370.2 236 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(azetidin-1- yl)ethanone 368.2 237 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(2-cyanopropyl)-N- ethylacetamide 423.2 238 68

B

3-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-methylpyrrolidin-2- one 368.2 239 68

B

3-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-phenylpiperidin-2-one 444.2 240 68

B

3-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4- chlorophenyl)pyrrolidin- 2-one 464.2 24160

A

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-methoxypyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-5- carbonitrile hydrochloride 382.2242 60

A

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((5-methoxypyrimidin-2-yl)methyl)-1H- benzo[d]imidazole-6- carbonitrile hydrochloride 382.2243 60

A

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((6-(trifluoromethyl)pyridin- 3-yl)methyl)-1H- benzo[d]imidazole-6-carbonitrile hydrochloride 419.2 244 60

A

2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1- ((6-(trifluoromethyl)pyridin- 3-yl)methyl)-1H- benzo[d]imidazole-5-carbonitrile hydrochloride 419.2 245 68

B

(S)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-methylpyrrolidin-2- one 368.2 246 68

B

(R)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-methylpyrrolidin-2- one 368.2 247 68

B

(S)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4- chlorophenyl)pyrrolidin- 2-one 464.2 24868

B

(R)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4- chlorophenyl)pyrrolidin- 2-one 464.2 24960

B

2-((3R,4R)-3-amino-4- fluoro-1-piperidinyl)-1- ((5-cyano-2-pyrazinyl)methyl)-1H- benzimidazole-6- carbonitrile 377.2 250 60

B

2-((3R,4R)-3-amino-4- fluoro-1-piperidinyl)-1- ((5-cyano-2-pyrazinyl)methyl)-1H- benzimidazole-5- carbonitrile 377.2 251 62

B

5-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-4,6- difluoro-1H-benzimidazol-1- yl)methyl)-2- pyrazinecarbonitrile 388.2 252 62

B

5-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,7- difluoro-1H-benzimidazol-1- yl)methyl)-2- pyrazinecarbonitrile 388.2 253 61

B

(3S)-1-(1-((5-fluoro-2- pyridinyl)methyl)-1H- benzimidazol-2-yl)-N-methyl-3- piperidinamine 340.2 254 61

B

(3S)-1-(1-((5-chloro-2- pyridinyl)methyl)-1H- benzimidazol-2-yl)-N-methyl-3- piperidinamine 356.2 255 61

B

6-((1R)-1-(2-((3S)-3- (methylamino)-1- piperidinyl)-1H- benzimidazol-1-yl)ethyl)-3- pyridinecarbonitrile 361.2 256 61

B

6-((1S)-1-(2-((3S)-3- (methylamino)-1- piperidinyl)-1H- benzimidazol-1-yl)ethyl)-3- pyridinecarbonitrile 361.2 257 62

B

(3R,4R)-1-(1-((5- chloro-2- pyrimidinyl)methyl)- 5,7-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 397.2 258 62

B

(3R,4R)-1-(1-((5- chloro-2- pyrimidinyl)methyl)- 4,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 397.2 259 68

B

(3R,4R)-1-(5,6- difluoro-1-((1-methyl- 1H-indazol-4- yl)methyl)-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 415.2 260 68

B

(3R,4R)-1-(5,6- difluoro-1-(5- quinolinylmethyl)-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 412.2 261 68

B

(3R,4R)-1-(5,6- difluoro-1-((1R)-1-(8- quinolinyl)ethyl)-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 426.2 262 68

B

(3R,4R)-1-(5,6- difluoro-1-((1S)-1-(8- quinolinyl)ethyl)-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 426.2 263 68

B

(3R,4R)-1-(1-((3-(3- chlorophenyl)-1,2- oxazol-5-yl)methyl)-5,6-difluoro-1H- benzimidazol-2-yl)-4- fluoro-3-piperidinamine 462.2 26468

B

(3R,4R)-1-(5,6- difluoro-1-((1-methyl- 1H-indazol-7- yl)methyl)-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 415.2 265 68

B

(3R,4R)-1-(1-(2,6- dichlorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 429.0 266 61

B

1-(1-azetidinyl)-2-(2- ((3S)-3-(methylamino)- 1-piperidinyl)-1H-benzimidazol-1- yl)ethanone 328.2 267 63

B

6-((1R)-1-(4,6-difluoro- 2-((4aR,8aR)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 268 63

B

6-((1R)-1-(4,6-difluoro- 2-((4aS,8aS)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 269 63

B

6-((1S)-1-(4,6-difluoro- 2-((4aS,8aS)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 270 63

B

6-((1S)-1-(4,6-difluoro- 2-((4aR,8aR)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 271 63

B

6-((1R)-1-(5,7-difluoro- 2-((4aR,8aR)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 272 63

B

6-((1R)-1-(5,7-difluoro- 2-((4aS,8aS)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 273 63

B

6-((1S)-1-(5,7-difluoro- 2-((4aS,8aS)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 274 63

B

6-((1S)-1-(5,7-difluoro- 2-((4aR,8aR)- hexahydro-2H- pyrido[4,3-b][1,4]oxazin-6(5H)- yl)-1H-benzimidazol-1- yl)ethyl)-3-pyridinecarbonitrile 425.2 275 68

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 5,6-difluoro-1H-benzimidazol-1-yl)-N- methylacetamide 342.2 276 68

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 5,6-difluoro-1H-benzimidazol-1-yl)-1- (4- morpholinyl)ethanone 398.2 277 68

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 5,6-difluoro-1H-benzimidazol-1-yl)-1- (1- pyrrolidinyl)ethanone 382.2 278 68

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 5,6-difluoro-1H-benzimidazol-1-yl)- N,N-dimethylacetamide 356.2 279 68

B

(2R)-2-(2-((3R,4R)-3- amino-4-fluoro-1-yl)- piperidinyl)-5,6-difluoro-1H- benzimidazol-1-yl)- N,N- dimethylpropanamide 370.2 280 68

B

(2S)-2-(2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1-yl)- N,N- dimethylpropanamide 370.2 281 68

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 5,6-difluoro-1H-benzimidazol-1-yl)-1- (1-piperidinyl)ethanone 396.2 282 68

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 5,6-difluoro-1H-benzimidazol-1-yl)-N- ethylacetamide 356.2 283 64

B

1-((5-chloro-2- pyrimidinyl)methyl)-2- ((3R,4R)-4-fluoro-3-(methylamino)-1- piperidinyl)-1H- benzimidazole-6- carbonitrile 400.0284 64

B

1-((5-chloro-2- pyrimidinyl)methyl)-2- ((3R,4R)-4-fluoro-3-(methylamino)-1- piperidinyl)-1H- benzimidazole-5- carbonitrile 400.0285 69

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 6-chloro-1H-benzimidazol-1-yl)-1- (1-azetidinyl)ethanone 366.2 286 69

B

2-(2-((3R,4R)-3-amino- 4-fluoro-1-piperidinyl)- 5-chloro-1H-benzimidazol-1-yl)-1- (1-azetidinyl)ethanone 366.2 287 74

B

2-((3R,4S)-3-amino-4- fluoro-1-piperidinyl)-1- (2-(1-azetidinyl)-2-oxoethyl)-1H- benzimidazole-6- carbonitrile 357.2 288 74

B

2-((3R,4S)-3-amino-4- fluoro-1-piperidinyl)-1- (2-(1-azetidinyl)-2-oxoethyl)-1H- benzimidazole-5- carbonitrile 357.2 289 65

B

(3R,4R)-1-(1-((5- chloropyrimidin-2- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 379.0 290 65

B

(3R,4R)-1-(1-((5- chloropyrimidin-2- yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 379.0 291 71

A

(R)-6-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile 333.2 292 72

A

(R)-5-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)picolinonitrile 2,2,2-trifluoroacetate 333.0 293 72 A

(R)-1-(1-(isoquinolin-7- ylmethyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 358.2 294 72

A

(R)-1-(1-((1-methyl- 1H-indazol-7- yl)methyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 361.2 295 71

A

6-((R)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile hydrochloride 347.2 296 71

A

6-((S)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile hydrochloride 347.2 297 67

B

6-((R)-1-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)ethyl)nicotinonitrile hydrochloride 365.0 29867

B

6-((S)-1-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)ethyl)nicotinonitrile hydrochloride 365.0 29971

B

6-((R)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)propyl)nicotinonitrile hydrochloride 361.2 300 71

B

6-((S)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)propyl)nicotinonitrile hydrochloride 361.2 301 68

B

(3R,4R)-1-(5,6- difluoro-1-((5- fluoropyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 381.2 302 68

B

3-(1-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)ethyl)benzonitrile 400.2 303 68

B

(3R,4R)-1-(5,6- difluoro-1-((5- fluoropyrimidin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 381.0 304 76

B

(3R,4S)-1-(5,6-difluoro- 1-((5-fluoropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 380.2 305 77

B

(3R,4S)-4-fluoro-1-(1- ((5-fluoropyrimidin-2- yl)methyl)-6-(trifluoromethyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 413.2 30677

B

(3R,4S)-4-fluoro-1-(1- ((5-fluoropyrimidin-2- yl)methyl)-5-(trifluoromethyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 413.2 30778

B

(R)-1-(5,6-difluoro-1- ((5-fluoropyridin-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4,4-difluoropiperidin-3- amine 398.0 308 77

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- 1-(azetidin-1-yl)ethan- 1-one 400.2 309 77

B

2-(2-((3R,4S)-3-amino- 4-fluoropiperidin-1-yl)- 5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- 1-(azetidin-1-yl)ethan- 1-one 400.2 310 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(2,2- dimethylpyrrolidin-1- yl)ethan-1-one410.2 311 80

B

6-((2-((3R,4S)-3- amino-4- hydroxypiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 367.2 312 80

B

6-((2-((3R,4S)-3- amino-4- hydroxypiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1- yl)methyl)nicotinonitrile 367.2 313 71

A

4-((R)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile hydrochloride 346.2 314 71

A

4-((S)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile hydrochloride 346.2 315 71

A

(S)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1- yl)methyl)-3-fluorobenzonitrile hydrochloride 350.0 316 71

A

(S)-1-(1-(4- chlorobenzyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-aminehydrochloride 341.0 317 79

A

4-((R)-1-(2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)ethyl)benzonitrile hydrochloride 364.0 318 79

A

4-((S)-1-(2-((3R,4S)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)ethyl)benzonitrile hydrochloride 364.0 319 67

A

4-((R)-1-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)ethyl)benzonitrile hydrochloride 364.2 320 67

A

4-((S)-1-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1- yl)ethyl)benzonitrile hydrochloride 364.2 321 71

A

(S)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1- yl)methyl)-3-chlorobenzonitrile hydrochloride 366.0 322 68

B

(3R,4R)-1-(1-((1R)-1- (2,4- dichlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 453.2 323 68

B

(3R,4R)-1-(1-((1S)-1- (2,4- dichlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 453.2 324 68

B

(3R,4R)-1-(1-((1R)-1- (2-chlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 409.2 325 68

B

(3R,4R)-1-(1-((1S)-1- (2-chlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 409.2 326 68

B

(3R,4R)-1-(1-((1R)-1- (3-chlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 409.2 327 68

B

(3R,4R)-1-(1-((1S)-1- (3-chlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 409.2 328 68

B

(3R,4R)-1-(1-((1R)-1- (2,5- dichlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 443.0 329 68

B

(3R,4R)-1-(1-((1S)-1- (2,5- dichlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 443.0 330 68

B

(3R,4R)-1-(1-((1R)-1- (2,4- difluorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 411.2 331 68

B

(3R,4R)-1-(1-((1S)-1- (2,4- difluorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 411.2 332 68

B

(3R,4R)-1-(1-((1R)-1- (3,4- dichlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 443.0 333 68

B

(3R,4R)-1-(1-((1S)-1- (3,4- dichlorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 443.0 334 68

B

(3R,4R)-1-(1-((1R)- (2,5- difluorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 411.2 335 68

B

(3R,4R)-1-(1-((1S)-1- (2,5- difluorophenyl)ethyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 411.2   336 b 68

B

(3R,4R)-1-(5,6- difluoro-1-((1R)-1-(4- (trifluoromethyl)phenyl)ethyl)-1H- benzimidazol-2-yl)-4- fluoro-3-piperidinamine 443.2   337 b68

B

(3R,4R)-1-(5,6- difluoro-1-((1R)-1-(4- (trifluoromethoxy)phenyl)ethyl)-1H- benzimidazol-2-yl)-4- fluoro-3-piperidinamine 459.2 338 68

B

(3R,4R)-1-(1-(5-chloro-2- 2- (trifluoromethoxy)benzyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 479.2 339 68

B

(3R,4R)-1-(5,6- difluoro-1-(4-(1H-1,2,4- triazol-1-yl)benzyl)-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 428.2 340 68

B

2-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)-5- chlorobenzonitrile 420.2 341 68

B

(3R,4R)-1-(1-(2,4- dichlorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 429.2 342 68

B

4-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)-3- (difluoromethoxy)benzo- nitrile 452.2 34368

B

(3R,4R)-1-(1-(2,5- dichlorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 429.0 344 68

B

(3R,4R)-1-(1-(4-(1,1- difluoroethyl)benzyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 425.2 345 68

B

4-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)-2- methylbenzonitrile 400.2 346 68

B

4-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)-2- chlorobenzonitrile 420.2 347 68

B

2-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)-4- chlorobenzonitrile 420.2 348 68

B

(3R,4R)-1-(1-(2- (difluoromethoxy)benzyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 427.2 349 68

B

(3R,4R)-1-(1-(3-chloro- 4-fluorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 413.0 350 68

B

(3R,4R)-1-(1-(4-chloro- 2-methoxybenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 425.2 351 68

B

(3R,4R)-1-(1-(2,4- difluorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 397.2 352 68

B

(3R,4R)-1-(5,6- difluoro-1-(2- (trifluoromethyl)benzyl)-1H-benzimidazol-2- yl)-4-fluoro-3- piperidinamine 429.2 353 68

B

2-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)benzonitrile 386.2 354 68

B

(3R,4R)-1-(1-(2- chlorobenzyl)-5,6- difluoro-1H- benzimidazol-2-yl)-4-fluoro-3-piperidinamine 395.0 355 68

B

(3R,4R)-1-(1-(2-chloro- 4-fluorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 413.0 356 68

B

(3R,4R)-1-(5,6- difluoro-1-(4-fluoro-2- (trifluoromethyl)benzyl)-1H-benzimidazol-2- yl)-4-fluoro-3- piperidinamine 447.2 357 68

B

(3R,4R)-1-(1-(3,4- difluorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 397.2 358 68

B

(3R,4R)-1-(1-(4-chloro- 2-fluorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 413.0 359 68

B

(3R,4R)-1-(1-(3,4- dichlorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 429.0 360 68

B

(3R,4R)-1-(1-(4-chloro- 3-fluorobenzyl)-5,6- difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 413.2 361 68

B

(3R,4R)-1-(5,6- difluoro-1-(4- (trifluoromethyl)benzyl)-1H-benzimidazol-2- yl)-4-fluoro-3- piperidinamine 429.2 362 68

B

(3R,4R)-1-(5,6- difluoro-1-(4- (trifluoromethoxy)benzyl)-1H-benzimidazol-2- yl)-4-fluoro-3- piperidinamine 445.2 363 68

B

(3R,4R)-1-(1-(4- (difluoromethyl)benzyl)- 5,6-difluoro-1H-benzimidazol-2-yl)-4- fluoro-3-piperidinamine 411.2 364 68

B

(3R,4R)-1-(5,6- difluoro-1-(3- (trifluoromethoxy)benzyl)-1H-benzimidazol-2- yl)-4-fluoro-3- piperidinamine 445.2 365 68

B

(3R,4R)-1-(5,6- difluoro-1-(3- (trifluoromethyl)benzyl)-1H-benzimidazol-2- yl)-4-fluoro-3- piperidinamine 429.2 366 68

B

3-((2-((3R,4R)-3- amino-4-fluoro-1- piperidinyl)-5,6- difluoro-1H-benzimidazol-1- yl)methyl)benzonitrile 386.2 367 68

B

(3R,4R)-1-(1-(3- chlorobenzyl)-5,6- difluoro-1H- benzimidazol-2-yl)-4-fluoro-3-piperidinamine 395.2 368 71

B

(S)-1-(1-(4- fluorobenzyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine325.3 369 71

B

(S)-1-(1-(4-(1,2,4- oxadiazol-3-yl)benzyl)- 1H-benzo[d]imidazol-2-yl)piperidin-3-amine 375.2 370 72

B

(R)-1-(1-(4- (methylsulfonyl)benzyl)- 1H-benzo[d]imidazol-2-yl)piperidin-3-amine 385.2 371 72

B

(R)-1-(1-(4-(1H-1,2,4- triazol-1-yl)benzyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 374.0 372 72

A

(R)-2-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 332.2 373 72

A

(R)-1-(1-(2,6- dichlorobenzyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 376.2 374 72

A

(R)-1-(1-(2- chlorobenzyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine341.2 375 72

A

(R)-1-(1-(4- (trifluoromethyl)benzyl)- 1H-benzo[d]imidazol-2-yl)piperidin-3-amine 375.2 376 72

A

(R)-1-(1-(4- (trifluoromethoxy)benzyl)- 1H- benzo[d]imidazol-2-yl)piperidin-3-amine 391.0 377 72

A

(R)-1-(1-(4- chlorobenzyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine341.2 378 72

A

(R)-1-(1-(3- chlorobenzyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine341.2 379 72

A

(R)-1-(1-(4-(1,1- difluoroethyl)benzyl)- 1H-benzo[d]imidazol-2-yl)piperidin-3-amine 371.2 380 72

A

(R)-2-(4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)phenyl)-2- methylpropanenitrile 374.2 381 72

A

(R)-1-(1-(4- (difluoromethyl)benzyl)- 1H-benzo[d]imidazol-2-yl)piperidin-3-amine 357.0 382 72

A

(R)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1- yl)methyl)-N-methylbenzamide 364.2 383 72

A

(R)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1- yl)methyl)-3-fluorobenzonitrile 350.2 384 72

A

(R)-2-(4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)phenoxy) acetonitrile 362.2 385 72

A

(R)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)-N,N- dimethylbenzenesulfon- amide 414.2 386 72

A

(R)-1-(1-(4- methylbenzyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine321.2 387 72

A

(R)-1-(1-(4- fluorobenzyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine324.4 388 72

A

(R)-1-(1-((1-methyl- 1H-indazol-7- yl)methyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 361.2 389 72

A

(R)-1-(1-(2,4- difluorobenzyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 343.2 390 72

A

(R)-1-(1-(3,4- difluorobenzyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 343.2 391 72

A

(R)-1-(1-(4-chloro-3- fluorobenzyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 359.2 392 72

A

(R)-1-(1-((3-(3- chlorophenyl)isoxazol- 5-yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 408.2 393 72

A

(R)-1-(1-(3-chloro-4- methoxybenzyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 371.2 394 72

A

(R)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1- yl)methyl)-3-chlorobenzonitrile 366.2 395 72

A

(R)-1-(1-(2,4- dichlorobenzyl)-1H- benzo[d]imidazol-2-yl)piperidin-3-amine 376.2 396 72

A

(R)-4-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1- yl)methyl)-3-methoxybenzonitrile 362.2 397 72

A

(R)-2-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1- yl)methyl)-5-chlorobenzonitrile 366.2 398 72

A

4-((R)-1-(2-((R)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile 347.2 399 71

A

4-(1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)ethyl)benzonitrile 346.2 400 72

A

(R)-3-((2-(3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)methyl)benzonitrile 332.2 494

B

(3R,4R)-3-amino-1-(1- ((5-chloropyrimidin-2- yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2- yl)piperidin-4-ol 377.2 495

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1-yl)- 1-morpholinoethanone 396.2 496 75

B

(3R,4R)-3-amino-1-(1- ((5-chloropyrimidin-2- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2- yl)piperidin-4-ol 377.2 497 69

B

-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-chloro-1H-benzo[d]imidazol-1-yl)- 1-morpholinoethanone 396.2 498 68

B

(3R,4R)-1-(1-((R)-1-(5- chloropyrimidin-2- yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2- yl)-4-fluoropiperidin-3- amine 411.0 499 81

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6-(trifluoromethyl)-1H- imidazo[4,5-b]pyridin- 1-yl)methyl)nicotinonitrile 420.2 500 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide424.2 501 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(thiazol-2- yl)acetamide 425.2 502 69

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 354.2 503 65

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- 1-(azetidin-1-yl)ethan- 1-one 350.2 504 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(3- (trifluoromethyl)piperidin-1-yl)ethan-1-one 464.2 505 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(6,7- dihydrothieno[3,2- c]pyridin-5(4H)-yl)ethan-1-one 450.2 506 69

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-chloro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 354.2 507 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(2- methyl)morpholino)ethan- 1-one 412.2 50868

B

(3R,4R)-1-(1-((R)-1-(5- chloropyrimidin-2- yl)ethyl)-5,6-difluoro-1H-benzo[d]imidazol-2- yl)-4-fluoropiperidin-3- amine 411.0 509 82

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-fluoro-7-methoxy-1H-benzo[d]imidazol-1- yl)-N-methyl-N-(2,2,2- trifluoroethyl)acetamide436.2 510 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(azocan-1-yl)ethan-1- one 424.2 511 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4-(pyrazin-2- yl)piperazin-1-yl)ethan- 1-one475.2 512 68

B

methyl 1-(2-(2- ((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6-difluoro-1H- benzo[d]imidazol-1- yl)acetyl)piperidine-4- carboxylate454.2 513 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(2- ethylmorpholino)ethan- 1-one 426.2 514 65

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1-yl)- 1-(azetidin-1-yl)ethan- 1-one 350.2 515 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(1,1-dioxido-2,3- dihydrothiophen-3-yl)-N-phenylacetamide 520.2 516 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4-methylpiperidin-1- yl)ethan-1-one 410.2 51765

B

(3R,4R)-4-fluoro-1-(6- fluoro-1-((4- methoxypyridin-2- yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 375.2 518 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(2- ethylmorpholino)ethan- 1-one 426.2 519 81

B

6-((2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)-6-(trifluoromethyl)-3H- imidazo[4,5-b]pyridin- 3-yl)methyl)nicotinonitrile 420.2 520 65

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)-1-(azetidin-1- yl)ethan-1-one 332.2 521 68

B

1-(2-(2-(3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)piperidine-2- carboxamide 439.2 522 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(1,1- dioxidotetrahydrothiophen-3-yl)-N-(thiophen-2- ylmethyl)acetamide 542.2 523 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1- (octahydroisoquinolin- 2(1H)-yl)ethan-1-one450.2 524 65

B

(3R,4R)-4-fluoro-1-(5- fluoro-1-((4- methoxypyridin-2- yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 375.2 525 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(1,1- dioxidotetrahydrothiophen- 3-yl)-N-methylacetamide 460.2 526 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-cyclopropyl-N-(1,1- dioxidotetrahydrothiophen-3-yl)acetamide 486.2 527 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(1,1- dioxidotetrahydrothiophen- 3-yl)-N-ethylacetamide 474.2 528 68

B

4-(2-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)piperazin-2- one 411.2 529 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4-(pyrrolidine-1- carbonyl)piperidin-1-yl)ethan-1-one 493.2 530 68

B

1-(2-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)piperidine-3- carboxamide 439.2 531 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4- (cyclopropanecarbonyl)piperazin-1-yl)ethan-1- one 465.2 532 68

B

1-(2-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)piperidine-4- carbaxamide 439.2 533 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(2-cyanopropan-2- yl)-N-methylacetamide 409.2534 68

B

1-(2-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-N- methylpiperidine-4- carboxamide 453.2535 68

B

N-(1-(2-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)piperidin-3- yl)acetamide 453.2 536 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4-(piperidine-1- carbonyl)piperidin-1-yl)ethan-1-one 507.2 537 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4-(azepane-1- carbonyl)piperidin-1-yl)ethan-1-one 521.2 538 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(1,1- dioxidotetrahydrothiophen- 3-yl)-N-(2-methoxyethyl)acetamide 504.2 539 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(4-(3- methylpiperidine-1-carbonyl)piperidin-1- yl)ethan-1-one 521.2 540 68

B

1-(4-acetylpiperazin-1- yl)-2-(2-((3R,4R)-3- amino-4-fluoropiperidin-1-yl)- 5,6-difluoro-1H- benzo[d]imidazol-1-yl)ethan-1-one 439.2 541 68

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-(1,1- dioxidotetrahydrothiophen- 3-yl)-N-((tetrahydrofuran-2- yl)methyl)acetamide 530.2 542 68

B

1-(2-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-N-isopropyl- N-methylpiperidine-4-carboxamide 495.2 543 68

B

2-(2-((3R,4R)-3-amino- 4-methoxypiperidin-1- yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide418.2 544 82

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-fluoro-7-methoxy-1H-benzo[d]imidazol-1- yl)-N-methyl-N-(2,2,2- trifluoroethyl)acetamide436.2 545 82

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-fluoro-4-methoxy-1H-benzo[d]imidazol-1- yl)-1-morpholinoethan- 1-one 410.2 546 82

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-fluoro-7-methoxy-1H-benzo[d]imidazol-1- yl)-1-morpholinoethan- 1-one 410.2 547 68

A

(R)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1- cyclopropylpyrrolidin- 2-one 394.2 548 68

A

(S)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(tetrahydro-2H-pyran- 4-yl)pyrrolidin-2-one438.2 549 68

A

(S)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1- cyclopropylpyrrolidin- 2-one 394.2 550 68

A

(R)-3-(2-((3R,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(tetrahydro-2H-pyran- 4-yl)pyrrolidin-2-one438.2 551 68

B

(3R,4R)-1-(5,6- difluoro-1-((5- methylthiazol-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 382.2 552 62

B

(3R,4R)-1-(4,6- difluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 383.2553 68

B

(3R,4R)-1-(5,6- difluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 383.2554 83

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide456.2 555 84

B

(3R,4R)-1-(1-((5- chloropyrimidin-2- yl)methyl)-6-fluoro-1H-imidazo[4,5-b]pyridin- 2-yl)-4-fluoropiperidin- 3-amine 380.0 556 62

B

(3R,4R)-1-(4,6- difluoro-1-((5- (methylsulfonyl)pyridin-2-yl)methyl)-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine440.2 557 62

B

(3R,4R)-1-(1-((5- (difluoromethyl)-1,3,4- thiadiazol-2-yl)methyl)-4,6-difluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine419.2 558 62

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 4,6-difluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide424.2 559 69

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-chloro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide422.2 560 68

B

(3R,4R)-1-(1-((5- (difluoromethyl)-1,3,4- thiadiazol-2-yl)methyl)-5,6-difluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine419.0 561 65

B

(3R,4R)-4-fluoro-1-(6- fluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 365.2 562 68

B

(3R,4R)-1-(5,6- difluoro-1-((5- (methylsulfonyl)pyridin-2-yl)methyl)-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine440.2 563 83

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 388.2 564 68

B

(3R,4R)-1-(5,6- difluoro-1-((5- methylisoxazol-3- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 366.2 565 62

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 4,6-difluoro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 356.2 566 65

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 6-fluoro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 338.2 567 68

B

(3R,4R)-1-(5,6- difluoro-1-((5- methyloxazol-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 366.2 568 68

B

(3R,4R)-1-(5,6- difluoro-1-((4- methylthiazol-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 382.0 569 65

B

(3R,4R)-4-fluoro-1-(6- fluoro-1-((3- (trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)- 1H-benzo[d]imidazol-2- yl)piperidin-3-amine403.2 570 69

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-chloro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide422.2 571 68

B

(3R,4R)-1-(5,6- difluoro-1-((5-methyl- 1,3,4-oxadiazol-2- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 367.2 572 68

B

(3R,4R)-1-(5,6- difluoro-1-((5-methyl- 1,2,4-oxadiazol-3- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 367.2 573 65

B

(3R,4R)-1-(1-((5- (difluoromethyl)-1,3,4- thiadiazol-2-yl)methyl)-6-fluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 401.2574 84

B

(3R,4R)-4-fluoro-1-(6- fluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- imidazo[4,5-b]pyridin- 2-yl)piperidin-3-amine 366.2 57568

B

(3R,4R)-1-(1-((4,5- dimethyloxazol-2- yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2- yl)-4-fluoropiperidin-3- amine 380.2 576 65

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-fluoro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 338.2 577 68

B

(3R,4R)-1-(1-((5-ethyl- 1,2,4-oxadiazol-3- yl)methyl)-5,6-difluoro-1H-benzo[d]imidazol-2- yl)-4-fluoropiperidin-3- amine 381.2 578 68

B

(3R,4R)-1-(1-((5- cyclopropyl-1,2,4- oxadiazol-3-yl)methyl)-5,6-difluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine393.2 579 68

B

(3R,4R)-1-(5,6- difluoro-1-((3- methylisoxazol-5- yl)methyl)-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 366.2 580 83

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide456.2 581 68

B

(3R,4R)-1-(1-((5- cyclopropyl-1,3,4- oxadiazol-2-yl)methyl)-5,6-difluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine393.2 582 65

B

(3R,4R)-4-fluoro-1-(5- fluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 365.2 583 84

B

(3R,4R)-1-(3-((5- chloropyrimidin-2- yl)ethyl)-6-fluoro-3H-imidazo[4,5-b]pyridin- 2-yl)-4-fluoropiperidin- 3-amine 380.2 584 65

B

(3R,4R)-4-fluoro-1-(5- fluoro-1-((3- (trifluoromethyl)-1,2,4-oxadiazol-5-yl)methyl)- 1H-benzo[d]imidazol-2- yl)piperidin-3-amine403.0 585 65

B

(3R,4R)-4-fluoro-1-(6- fluoro-1-((4-methyl-2- phenylthiazol-5-yl)methyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 440.2 586 68

B

(3R,4R)-1-(1-((4,5- dimethyl-4H-1,2,4- triazol-3-yl)methyl)-5,6-difluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine380.2 587 65

B

(3R,4R)-1-(1-((5- (difluoromethyl)-1,3,4- thiadiazol-2-yl)methyl)-5-fluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 401.2588 85

B

(R)-4,4-difluoro-1-(6- fluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 383.2 589 65

B

(3R,4R)-1-(1-((2,4- dimethylthiazol-5- yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 378.2 590 84

B

(3R,4R)-4-fluoro-1-(6- fluoro-3-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-3H- imidazo[4,5-b]pyridin- 2-yl)piperidin-3-amine 366.2 59162

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,7-difluoro-1H-benzo[d]imidazol-1-yl)- N-methyl-N-(2,2,2- trifluoroethyl)acetamide424.2 592 83

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 388.2 593 65

B

(3R,4R)-4-fluoro-1-(5- fluoro-1-((4-methyl-2- phenylthiazol-5-yl)methyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 440.2 594 62

B

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,7-difluoro-1H-benzo[d]imidazol-1-yl)- N,N-dimethylacetamide 356.2 595 62

B

(3R,4R)-1-(5,7- difluoro-1-((5- (methylsulfonyl)pyridin-2-yl)methyl)-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine440.2 596 65

B

(3R,4R)-1-(1-((2,4- dimethylthiazol-5- yl)methyl)-5-fluoro-1H-benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine 378.2 597 85

B

(R)-4,4-difluoro-1-(5- fluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- benzo[d]imidazol-2- yl)piperidin-3-amine 383.2 598 62

B

(3R,4R)-1-(1-((5- (difluoromethyl)-1,3,4- thiadiazol-2-yl)methyl)-5,7-difluoro-1H- benzo[d]imidazol-2-yl)- 4-fluoropiperidin-3- amine419.2 599 62

B

(3R,4R)-1-(5,7- difluoro-1-((5-methyl- 1,3,4-thiadiazol-2-yl)methyl)-1H- benzo[d]imidazal-2-yl)- 4-fluoropiperidin-3- amine 383.2^(a)Boc was removed using TFA. The free base was redissolved in DCM, andHCl was added to crash out the HCl salt. b unspecified stereochemistrydenotes a mixture of enantiomers or diastereomers.

TABLE 6 Characterization data for compounds made following schemes 9-10The column “Separation Stage” indicates after which process stepregioisomers formed due to asymmetric benzimidazole substitution at R¹in Scheme 10 were separated during the preparation of the tabulatedfinal compound. (I = after preparation of theN-aralkyl-2-piperidinyl-benzimidazole intermediate in the first step ofScheme 10 (where at least one R¹ is not hydrogen); B = prior to bocdeprotection; or F = final compound). SFC Isomer Ex. Freq., ¹HNMR DataSeparation Separation # Solvent (δ ppm) Stage Conditions 187 500 MHz8.80 (s, 2H), 7.65-7.69 (m, 1H), 7.54-7.61 (m, 1H), B Chiralpak d₄- 7.49(d, J = 8.30 Hz, 1H), 5.57 (s, 2H), 4.42-4.60 (m, AD-H, 25% MeOH 1H),3.72-3.80 (m, 1H), 3.64 (br d, J = 13.23 Hz, IPA, peak 1 1H), 3.15-3.27(m, 2H), 3.06 (dd, J = 9.21, 12.59 Hz, 1H), 2.13-2.27 (m, 1H), 1.80-1.99(m, 1H) 188 500 MHz 8.68-8.74 (s, 2H), 7.47-7.52 (m, 1H), 7.14-7.20 (m,— — d₄- 2H), 7.08-7.13 (m, 1H), 5.53 (s, 2H), 4.34-4.52 (m, MeOH 1H),3.64 (dtd, J = 1.95, 4.14, 12.36 Hz, 1H), 3.48- 3.57 (m, 1H), 3.04-3.21(m, 2H), 2.98 (dd, J = 8.82, 12.20 Hz, 1H), 2.12-2.25 (m, 1H), 1.82-1.92(m, 1H) 189 400 MHz 8.40 (d, J = 2.90 Hz, 1H), 7.47-7.58 (m, 2H), 7.21 —— d₄- (dd, J = 4.35, 8.71 Hz, 1H), 7.13-7.17 (m, 1H), 7.06- MeOH 7.13(m, 2H), 4.32-4.55 (m, 1H), 3.62 (dtd, J = 1.66, 4.17, 12.39 Hz, 1H),3.41-3.52 (m, 1H), 3.04-3.18 (m, 2H), 2.92-3.01 (m, 1H), 2.07-2.22 (m,1H), 1.80-1.97 (m, 1H) 190 400 MHz 8.40 (d, J = 2.90 Hz, 1H), 7.61 (dt,J = 2.90, 8.50 Hz, B Chiralpak d₄- 1H), 7.52-7.56 (m, 2H), 7.42-7.46 (m,1H), 7.40 AD-H, 20% MeOH (dd, J = 4.35, 8.71 Hz, 1H), 5.46 (s, 2H),4.32-4.54 MeOH, Peak 1 (m, 1H), 3.67-3.75 (m, 1H), 3.55-3.65 (m, 1H),3.21 (ddd, J = 2.90, 10.21, 12.80 Hz, 1H), 3.06-3.14 (m, 1H), 2.98-3.05(m, 1H), 2.10-2.25 (m, 1H), 1.89 (ddd, J = 3.52, 9.69, 13.53 Hz, 1H) 191400 MHz 8.39 (d, J = 2.90 Hz, 1H), 7.75-7.78 (m, 1H), 7.61 B Chiralpakd₄- (dt, J = 2.90, 8.50 Hz, 1H), 7.35-7.42 (m, 2H), 7.27 AD-H, 20% MeOH(d, J = 8.29 Hz, 1H), 5.45-5.50 (m, 2H), 4.32-4.54 MeOH, Peak 2 (m, 1H),3.68 (dtd, J = 1.66, 4.02, 12.28 Hz, 1H), 3.51-3.63 (m, 1H), 3.15-3.25(m, 1H), 3.10 (ddd, J = 3.94, 7.72, 9.48 Hz, 1H), 2.96-3.06 (m, 1H),2.13- 2.27 (m, 1H), 1.81-1.97 (m, 1H) 192 500 MHz 8.98 (s, 2H),7.42-7.47 (m, 1H), 7.07-7.15 (m, 2H), — — d₄- 7.01-7.06 (m, 1H), 5.49(s, 2H), 4.33-4.51 (m, 1H), MeOH 3.37-3.50 (m, 2H), 2.99-3.07 (m, 2H),2.82 (br dd, J = 8.95, 12.07 Hz, 1H), 2.00-2.16 (m, 1H), 1.65- 1.79 (m,1H) 193 400 MHz 8.97 (s, 2H), 7.60-7.67 (m, 1H), 7.16-7.23 (m, 1H), — —CDCl₃ 7.03-7.15 (m, 2H), 5.45-5.56 (m, 2H), 4.29-4.56 (m, 1H), 3.64-3.76(m, 1H), 3.51-3.63 (m, 1H), 3.14- 3.33 (m, 2H), 3.03 (dd, J = 8.60,12.54 Hz, 1H), 2.08- 2.24 (m, 1H), 1.83-2.03 (m, 1H) 194 400 MHz8.36-8.39 (m, 2H), 7.60 (d, J = 8.50 Hz, 1H), 7.14- — — CDCl₃ 7.20 (m,2H), 7.06-7.14 (m, 1H), 5.36 (d, J = 2.07 Hz, 2H), 4.34-4.56 (m, 1H),3.90 (s, 3H), 3.63-3.78 (m, 2H), 3.14-3.31 (m, 2H), 3.04 (dd, J = 8.40,12.54 Hz, 1H), 2.11-2.25 (m, 1H), 1.90-2.05 (m, 1H) 195 400 MHz 8.76 (s,2H), 7.44-7.54 (m, 1H), 7.06-7.19 (m, 3H), — — d₄- 5.50 (br s, 2H),4.32-4.53 (m, 1H), 3.62 (br d, MeOH J = 12.23 Hz, 1H), 3.51 (br d, J =12.02 Hz, 1H), 3.02- 3.21 (m, 2H), 2.89-3.01 (m, 1H), 2.12-2.26 (m, 1H),1.81-1.98 (m, 1H) 196 500 MHz 8.70-8.75 (m, 2H), 7.65-7.69 (m, 1H), 7.58(d, B Chiralpak d₄- J = 8.30 Hz, 1H), 7.45-7.52 (m, 1H), 5.58 (s, 2H),AD-H, 20% MeOH 4.43-4.65 (m, 1H), 3.76-3.83 (m, 1H), 3.67 (br d, MeOH,peak 1 J = 12.98 Hz, 1H), 3.16-3.32 (m, 2H), 3.09 (dd, J = 9.34, 12.46Hz, 1H), 2.15-2.29 (m, 1H), 1.86- 1.99 (m, 1H) 197 500 MHz 8.72 (s, 2H),7.77-7.82 (m, 1H), 7.41-7.45 (m, 1H), B Chiralpak d₄- 7.32-7.38 (m, 1H),5.59 (s, 2H), 4.33-4.51 (m, 1H), AD-H, 20% MeOH 3.65-3.71 (m, 1H),3.53-3.63 (m, 1H), 3.16-3.24 (m, MeOH, peak 2 1H), 3.05-3.14 (m, 1H),2.96-3.04 (m, 1H), 2.14- 2.28 (m, 1H), 1.89 (ddd, J = 3.63, 9.67, 13.43Hz, 1H) 198 400 MHz 8.70-8.89 (m, 1H), 7.72-7.98 (m, 1H), 7.17-7.54 (m,B Chiralpak d₄- 2H), 5.31-5.67 (m, 2H), 4.39-4.66 (m, 1H), 3.57- AD-H,25% MeOH 3.82 (m, 2H), 3.01-3.25 (m, 3H), 2.15-2.35 (m, 1H), IPA, peak 21.93 (td, J = 1.22, 9.80 Hz, 1H) 199 400 MHz 8.90 (d, J = 1.45 Hz, 1H),8.75-8.78 (m, 1H), 7.48- — — d₄- 7.56 (m, 1H), 7.08-7.23 (m, 4H), 5.66(s, 2H), 3.39- MeOH 3.59 (m, 3H), 3.13-3.30 (m, 2H), 2.25-2.40 (m, 1H),2.04-2.25 (m, 1H) 200 400 MHz 8.88 (s, 2H), 7.63-7.68 (m, 1H), 7.53-7.59(m, 1H), B Chiralpak d₄- 7.45-7.50 (m, 1H), 5.53 (s, 2H), 4.36-4.58 (m,1H), AD-H, 25% MeOH 3.72 (br dd, J = 1.45, 12.65 Hz, 1H), 3.58-3.66 (m,IPA, peak 1 1H), 3.10-3.26 (m, 2H), 2.99-3.07 (m, 1H), 2.13- 2.27 (m,1H), 1.82-1.95 (m, 1H) 201 400 MHz 8.86-8.90 (m, 2H), 7.80-7.84 (m, 1H),7.45 (dd, B Chiralpak d₄- J = 1.24, 8.29 Hz, 1H), 7.34-7.39 (m, 1H),5.56 (s, AD-H, 25% MeOH 2H), 4.33-4.53 (m, 1H), 3.62-3.70 (m, 1H), 3.53-IPA, peak 1 3.60 (m, 1H), 3.14-3.23 (m, 1H), 3.02-3.13 (m, 1H),2.94-3.02 (m, 1H), 2.18-2.26 (m, 1H), 1.80-1.96 (m, 1H) 202 400 MHz 9.11(s, 1H), 8.92 (s, 1H), 8.30-8.39 (m, 3H), 7.47- — — CDCl₃ 7.53 (m, 1H),7.23 (d, J = 7.88 Hz, 1H), 7.14-7.19 (m, 1H), 7.11 (d, J = 7.26 Hz, 1H),5.68 (s, 2H), 4.81- 4.92 (m, 1H), 3.59-3.74 (m, 2H), 3.45-3.55 (m, 1H),3.03-3.16 (m, 2H), 2.14-2.24 (m, 1H), 1.80-1.93 (m, 1H) 203 500 MHz 8.79(s, 2 H), 7.75-7.89 (m, 1 H), 7.45 (dd, J = 8.30, B Chiralpak d₄- 1.30Hz, 1 H), 7.36 (d, J = 8.04 Hz, 1 H), 5.55-5.60 OJ, 15% MeOH (m, 2 H),3.44-3.54 (m, 2 H), 3.35-3.42 (m, 2 H), MeOH, peak 1 3.06-3.25 (m, 3 H),1.89-2.18 (m, 2 H) 204 500 MHz 8.80 (s, 2 H), 7.65-7.69 (m, 1 H),7.56-7.61 (m, 1 B Chiralpak d₄- H), 7.51 (dd, J = 8.30, 1.56 Hz, 1 H),5.57 (s, 2 H), OJ, 15% MeOH 3.37-3.57 (m, 3 H), 3.06-3.26 (m, 3 H),2.09- MeOH, peak 2 2.18 (m, 1 H), 1.90-2.08 (m, 2 H) 205 500 MHz 8.78(s, 2H), 7.39-7.48 (m, 1H), 6.99 (dd, J = 2.47, B Chiralpak d₄- 8.95 Hz,1H), 6.90-6.95 (m, 1H), 5.48 (s, 2H), 3.64 AD-H, 25% MeOH (dd, J = 1.82,7.79 Hz, 1H), 3.42-3.53 (m, 2H), 3.05 MeOH, peak 2 (dt, J = 2.60, 12.07Hz, 1H), 2.83-2.90 (m, 2H), 2.01 (qd, J = 3.62, 13.01 Hz, 1H), 1.62-1.71(m, 1H) 206 500 MHz 8.75-8.79 (m, 2H), 7.12-7.22 (m, 2H), 6.82-6.93 (m,B Chiralpak d₄- 1H), 5.49 (s, 2H), 3.65-3.72 (m, 1H), 3.53-3.62 (m,AD-H, 25% MeOH 1H), 3.44-3.52, (m, 1H), 3.08 (dt, J = 2.60, 12.20 Hz,MeOH, peak 1 1H), 2.86-2.97 (m, 2H), 2.02 (qd, J = 3.61, 13.04 Hz, 1H),1.62-1.75 (m, 1H) 207 500 MHz 8.82-8.85 (m, 1H), 8.09-8.15 (m, 1H), 7.36(d, B Chiralpak d₄- J = 8.04 Hz, 1H), 7.18 (dd, J = 2.34, 9.34 Hz, 1H),AD-H, 25% MeOH 7.09 (dd, J = 4.54, 8.69 Hz, 1H), 6.87 (dt, J = 2.47,IPA, peak 1 9.28 Hz, 1H), 5.46-5.51 (m, 2H), 3.58-3.66 (m, 1H),3.46-3.54 (m, 1H), 3.38-3.44 (m, 1H), 3.02-3.14 (m, 1H), 2.73-2.90 (m,2H), 1.93-2.04 (m, 1H), 1.58- 1.72 (m, 1H) 208 500 MHz 8.84 (d, J = 1.30Hz, 1H), 8.09-8.18 (m, 1H), 7.41- B Chiralpak d₄- 7.47 (m, 1H), 7.37 (d,J = 8.30 Hz, 1H), 6.90-7.00 AD-H, 25% MeOH (m, 2H), 5.48 (s, 2H),3.50-3.59 (m, 1H), 3.36-3.47 IPA, peak 2 (m, 2H), 3.04 (dt, J = 2.60,11.94 Hz, 1H), 2.72-2.87 (m, 2H), 1.91-2.04 (m, 1H), 1.56-1.69 (m, 1H)209 400 MHz 8.56 (d, J = 2.1 Hz, 1H), 7.93 (dd, J = 2.5, 8.4 Hz, 1H), —— d₆- 7.52-7.31 (m, 2H), 7.25 (d, J = 8.4 Hz, 1H), 7.14-7.01 DMSO (m,2H), 5.47-5.34 (m, 2H), 3.55 (br dd, J = 3.2, 12.2 Hz, 1H), 3.27-3.18(m, 2H), 3.17-2.90 (m, 2H), 2.01-1.89 (m, 1H), 1.79 (br dd, J = 3.4, 9.9Hz, 1H), 1.64-1.45 (m, 2H) 210 400 MHz 8.72 (d, J = 1.66 Hz, 1H), 8.31(br s, 2H), 8.02 (d, — — d₆- J = 8.09 Hz, 1H), 7.83-7.89 (m, 1H), 7.57(d, J = 7.77 DMSO Hz, 1H), 7.27 (m, 3H), 5.54-5.61 (m, 2H), 3.70 (br dd,J = 2.80, 12.44 Hz, 1H), 3.48 (br s, 1H), 3.27- 3.44 (m, 2H), 3.07-3.16(m, 1H), 1.96-2.10 (m, 1H), 1.83-1.94 (m, 1H), 1.59-1.73 (m, 2H) 211 400MHz 8.92 (br s, 3H), 8.55 (d, J = 2.18 Hz, 1H), 8.03 (dd, — — d₆- J =2.49, 8.40 Hz, 1H), 7.67 (d, J = 8.40 Hz, 1H), 7.60 DMSO (d, J = 7.77Hz, 1H), 7.28-7.44 (m, 3H), 5.64-5.78 (m, 2H), 4.88-5.10 (m, 1H), 4.18(br d, J = 12.65 Hz, 1H), 3.77 (br d, J = 13.58 Hz, 1H), 3.54-3.63 (m,1H), 3.43-3.53 (m, 1H), 3.21-3.42 (m, 1H), 2.26- 2.37 (m, 1H), 1.82-1.94(m, 1H) 212 400 MHz 9.12 (br s, 3H), 8.94 (s, 1H), 8.40 (d, J = 8.19 Hz,— — d₆- 1H), 7.77 (d, J = 8.19 Hz, 1H), 7.61 (d, J = 7.88 Hz, DMSO 1H),7.25-7.39 (m, 3H), 5.72-5.93 (m, 2H), 4.03 (br d, J = 12.75 Hz, 2H),3.57-3.70 (m, 2H), 3.42 (br t, J = 10.78 Hz, 1H), 2.53-2.62 (m, 1H),2.23-2.38 (m, 1H) 213 500 MHz 8.57 (br s, 2H), 8.50-8.55 (m, 1H),7.94-8.00 (m, B Chiralpak DMSO- 2H), 7.43-7.51 (m, 2H), 7.35 (d, J =8.30 Hz, 1H), AD-H, 25% d₆ 5.54 (d, J = 7.66 Hz, 2H), 4.81 (dt, J =4.87, 9.11 Hz, IPA, peak 2 1H), 3.83-3.92 (m, 1H), 3.50-3.58 (m, 2H),3.16 (br dd, J = 10.19, 12.65 Hz, 1H), 3.06 (br t, J = 11.74 Hz, 1H),2.20 (br t, J = 9.54 Hz, 1H), 1.76-1.88 (m, 1H) 214 500 MHz 8.66 (br s,2H), 8.54 (d, J = 2.21 Hz, 1H), 7.98 (dd, B Chiralpak DMSO- J = 2.34,8.43 Hz, 1H), 7.78 (s, 1H), 7.57-7.63 (m, AD-H, 25% d₆ J = 8.30 Hz, 1H),7.51-7.57 (m, J = 8.30 Hz, 1H), 7.46 IPA, peak 2 (d, J = 8.43 Hz, 1H),5.49-5.62 (m, 2H), 4.79-4.99 (m, 1H), 3.95 (br d, J = 12.98 Hz, 1H),3.71-3.84 (m, 2H), 3.20 (br t, J = 11.48 Hz, 1H), 3.07 (br t, J = 11.81Hz, 1H), 2.21 (br t, J = 9.67 Hz, 1H), 1.80 (br t, J = 9.93 Hz, 1H) 215500 MHz 8.59 (br d, J = 2.47 Hz, 3H), 7.86-7.91 (m, 1H), 7.45 BChiralpak DMSO- (d, J = 7.91 Hz, 1H), 7.33 (s, 1H), 7.27-7.32 (m, 1H),IC, 20% d₆ 7.02-7.09 (m, 1H), 6.92-6.97 (m, 2H), 5.86 (q, methanol, peak1 J = 6.96 Hz, 1H), 4.76-4.99 (m, 1H), 3.65-3.76 (m, 2H), 3.37 (br s,1H), 3.14-3.22 (m, 1H), 3.07 (br t, J = 11.16 Hz, 1H), 2.19-2.27 (m,1H), 1.89-1.98 (m, 1H), 1.86 (d, J = 7.14 Hz, 3H) 216 500 MHz 8.63 (d, J= 1.95 Hz, 1H), 7.89 (br dd, J = 1.88, 8.50 B Chiralpak DMSO- Hz, 1H),7.47 (d, J = 7.92 Hz, 1H), 7.28 (d, J = 8.43 IC, 20% d₆ Hz, 1H), 7.07(t, J = 6.55 Hz, 1H), 6.94-7.00 (m, 2H), methanol, peak 2 5.87 (q, J =7.01 Hz, 1H), 4.71-4.90 (m, 1H), 3.66- 3.77 (m, 1H), 3.58-3.64 (m, 1H),3.40-3.48 (m, 1H), 3.02-3.18 (m, 2H), 2.20-2.28 (m, 1H), 1.96-2.02 (m,1H), 1.92 (d, J = 7.14 Hz, 3H) 217 500 MHz 8.56 (d, J = 2.34 Hz, 1H),8.53 (br s, 2H), 7.90 (dd, B Chiralcel DMSO- J = 2.47, 8.43 Hz, 1H),7.50 (dd, J = 7.59, 10.96 Hz, OZ-H, 15% d₆ 1H), 7.39 (d, J = 8.43 Hz,1H), 7.13 (dd, J = 7.33, methanol, peak 1 10.83 Hz, 1H), 5.83 (q, J =7.09 Hz, 1H), 4.75-4.93 (m, 1H), 3.65 (br dd, J = 4.48, 9.15 Hz, 2H),3.29 (br d, J = 11.94 Hz, 1H), 3.07-3.18 (m, 1H), 3.02 (br t, J = 11.03Hz, 1H), 2.16-2.24 (m, 1H), 1.85-1.92 (m, 1H), 1.83 (d, J = 7.14 Hz, 3H)218 500 MHz 8.65 (br s, 2H), 8.62 (d, J = 2.34 Hz, 1H), 7.94 (dd, BChiralcel DMSO- J = 2.47, 8.56 Hz, 1H), 7.55 (dd, J = 7.66, 11.03 Hz,OZ-H, 15% d₆ 1H), 7.39 (d, J = 8.56 Hz, 1H), 7.15-7.21 (m, 1H),methanol, peak 2 5.87 (q, J = 7.09 Hz, 1H), 4.80-4.97 (m, 1H), 3.62-3.79 (m, 2H), 3.16 (dd, J = 10.12, 11.94 Hz, 1H), 3.03 (br t, J = 11.55Hz, 1H), 2.25 (br t, J = 9.41 Hz, 1H), 1.94-2.03 (m, 1H), 1.91 (d, J =7.27 Hz, 3H) 219 500 MHz 8.58 (br s, 1H), 8.58 (br s, 2H), 7.91 (dd, J =2.47, B Regis Whelk- DMSO- 8.56 Hz, 1H), 7.44 (d, J = 8.36 Hz, 1H), 7.39(d, O s, s, 20% d₆ J = 8.39 Hz, 1H), 7.02-7.09 (m, 2H), 5.84 (q, J =7.09 methanol, peak 1 Hz, 1H), 4.73-4.97 (m, 1H), 3.68 (br dd, J = 4.09,10.70 Hz, 2H), 3.32 (br d, J = 11.42 Hz, 1H), 3.10- 3.21 (m, 1H), 3.05(br t, J = 11.03 Hz, 1H), 2.16-2.27 (m, 1H), 1.86-1.93 (m, 1H), 1.83 (d,J = 7.14 Hz, 3H) 220 500 MHz 8.64 (d, J = 2.46 Hz, 1H), 8.56 (br s, 2H),7.95 (dd, B Regis Whelk- DMSO- J = 2.47, 8.56 Hz, 1H), 7.46-7.51 (m, J =8.43 Hz, O s, s, 20% d₆ 1H), 7.35-7.43 (m, J = 8.56 Hz, 1H), 7.05-7.16(m, methanol, peak 2 2H), 5.87 (q, J = 7.14 Hz, 1H), 4.78-4.99 (m, 1H),3.75 (br d, J = 12.20 Hz, 2H), 3.37-3.50 (m, 1H), 3.13-3.21 (m, 1H),3.07 (br t, J = 11.55 Hz, 1H), 2.25 (br t, J = 9.34 Hz, 1H), 1.95-2.04(m, 1H), 1.92 (d, J = 7.14 Hz, 3H) 221 500 MHz 8.62 (br s, 1H), 8.60 (brs, 2H), 7.95 (dd, J = 2.47, B Regis Whelk- DMSO- 8.43 Hz, 1H), 7.54 (d,J = 1.56 Hz, 1H), 7.40 (d, O s, s, 20% d₆ J = 8.56 Hz, 1H), 6.97-7.05(m, 2H), 5.88 (q, J = 7.01 methanol, peak 3 Hz, 1H), 4.77-5.04 (m, 1H),3.76 (br s, 3H), 3.57 (s, 1H), 3.44 (br d, J = 12.07 Hz, 1H), 3.18-3.32(m, 1H), 3.13 (br t, J = 11.16 Hz, 1H), 2.23-2.32 (m, 1H), 1.92-2.01 (m,1H), 1.89 (d, J = 7.01 Hz, 3H) 222 500 MHz 8.62 (br d, J = 2.34 Hz, 3H),7.92 (dd, J = 2.47, 8.56 B Regis Whelk- DMSO- Hz, 1H), 7.54 (s, 1H),7.35 (d, J = 8.56 Hz, 1H), 6.99-7.05 O s, s, 20% d₆ (m, 2H), 5.87 (q, J= 7.01 Hz, 1H), 4.80- methanol, 5.01 (m, 1H), 3.78 (br dd, J = 5.00,11.87 Hz, 2H), peak 4 3.44-3.53 (m, 1H), 3.20 (dd, J = 10.38, 12.07 Hz,1H), 3.10 (br t, J = 11.48 Hz, 1H), 2.27 (br t, J = 9.41 Hz, 1H),1.95-2.04 (m, 1H), 1.92 (d, J = 7.14 Hz, 3H) 223 500 MHz 9.00 (s, 1H),8.63 (br s, 3H), 8.38 (dd, J = 1.69, 8.30 B Phenomenex Lux DMSO- Hz,1H), 7.58-7.70 (m, 3H), 7.52 (d, J = 8.30 Hz, Cellulose- d₆ 1H), 6.00(q, J = 7.01 Hz, 1H), 4.81-5.00 (m, 1H), 2, 20% 3.74-3.83 (m, 1H),3.65-3.74 (m, 1H), 3.42 (br d, isopropanol, peak 1 J = 11.68 Hz, 1H),3.24 (br dd, J = 9.80, 12.39 Hz, 1H), 3.13 (br t, J = 11.16 Hz, 1H),2.23-2.32 (m, 1H), 1.94 (br d, J = 7.14 Hz, 4H) 224 500 MHz 9.00 (s,1H), 8.69-8.73 (m, 2H), 8.36 (dd, J = 1.88, B Phenomenex Lux DMSO- 8.24Hz, 1H), 8.00 (s, 1H), 7.66 (d, J = 8.30 Hz, 1H), Cellulose- d₆ 7.41 (d,J = 8.43 Hz, 1H), 7.17 (d, J = 8.43 Hz, 1H), 2, 20% 6.04 (q, J = 6.96Hz, 1H), 4.86-5.04 (m, 1H), 3.77 (br isopropanol, peak 2 d, J = 12.72Hz, 1H), 3.65-3.73 (m, 1H), 3.42 (br d, J = 11.94 Hz, 1H), 3.26 (br dd,J = 9.60, 12.59 Hz, 1H), 3.12, (br t, J = 11.09 Hz, 1H), 2.25-2.34 (m,1H), 1.90-1.99 (m, 4H) 225 500 MHz 8.98-9.02 (m, 1H), 8.62 (br d, J =3.24 Hz, 2H), 8.36 B Phenomenex Lux DMSO- (dd, J = 1.88, 8.24 Hz, 1H),7.63 (dd, J = 3.18, 8.24 Cellulose- d₆ Hz, 2H), 7.59 (s, 1H), 7.52 (d, J= 8.17 Hz, 1H), 5.96 2, 20% (q, J = 6.96 Hz, 1H), 4.79-4.98 (m, 1H),3.74-3.86 isopropanol, peak 3 (m, 1H), 3.68-3.72 (m, 1H), 3.46 (br d, J= 11.94 Hz, 1H), 3.14-3.26 (m, 1H), 3.09 (br t, J = 12.00 Hz, 1H),2.19-2.30 (m, 1H), 1.97 (br d, J = 7.27 Hz, 4H) 226 500 MHz 8.92-8.96(m, 1H), 8.58 (br s, 3H), 8.28 (dd, J = 1.95, B Phenomenex Lux DMSO-8.30 Hz, 1H), 7.94 (s, 1H), 7.53 (d, J = 8.30 Hz, 1H), Cellulose- d₆7.34 (dd, J = 1.30, 8.43 Hz, 1H), 7.23 (s, 1H), 7.07- 2, 20% 7.16 (m,2H), 7.03 (s, 1H), 5.94 (q, J = 6.92 Hz, 1H), isopropanol, peak 44.72-4.93 (m, 1H), 3.68-3.79 (m, 1H), 3.58-3.68 (m, 1H), 3.40 (br d, J =12.85 Hz, 1H), 3.15 (br t, J = 11.35 Hz, 1H), 3.04 (br t, J = 11.74 Hz,1H), 2.20 (br t, J = 9.54 Hz, 1H), 1.95 (m, 1H), 1.91 (d, J = 7.01 Hz,3H) 227 500 MHz 8.54 (br d, J = 2.21 Hz, 1H), 8.52 (br s, 2H), 7.96 (dd,B — DMSO- J = 2.47, 8.43 Hz, 1H), 7.54 (dd, J = 7.53, 10.90 Hz, d₆ 1H),7.33-7.44 (m, 2H), 5.37-5.52 (m, 2H), 4.73- 4.92 (m, 1H), 3.75-3.83 (m,1H), 3.51-3.62 (m, 1H), 3.45 (br d, J = 12.20 Hz, 1H), 3.12 (br dd, J =10.64, 12.33 Hz, 1H), 3.01 (br t, J = 11.61 Hz, 1H), 2.14- 2.23 (m, 1H),1.76-1.90 (m, 1H) 228 500 MHz 8.52 (br s, 2H), 8.49 (d, J = 2.85 Hz,1H), 7.76 (dt, B — DMSO- J = 2.98, 8.69 Hz, 1H), 7.53 (dd, J = 7.40,11.03 Hz, d₆ 1H), 7.44 (t, J = 6.74 Hz, 1H), 7.37 (t, J = 8.28 Hz, 1H),5.38-5.51 (m, 2H), 4.73-4.95 (m, 1H), 3.75- 3.83 (m, 1H), 3.47 (br d, J= 12.98 Hz, 1H), 3.12 (dd, J = 10.19, 12.52 Hz, 1H), 3.01 (br t, J =11.42 Hz, 1H), 2.15-2.23 (m, 1H), 1.77-1.87 (m, 1H) 229 400 MHz 8.80 (brs, 2H), 8.52 (d, J = 2.38 Hz, 1H), 7.96 (dd, B Regis Whelk- DMSO- J =2.44, 8.45 Hz, 1H), 7.39 (d, J = 8.40 Hz, 1H), 7.21 O s, s, 15% d₆ (dd,J = 2.13, 9.17 Hz, 1H), 6.95 (t, J = 10.40 Hz, 1H), methanol, peak 15.45-5.58 (m, 2H), 3.76 (br d, J = 12.02 Hz, 1H), 3.31-3.47 (m, 2H),3.17-3.26 (m, 1H), 2.33 (m, 3H) 230 500 MHz 8.87 (br s, 2H), 8.55 (s,1H), 7.97 (br d, J = 8.17 Hz, B Regis Whelk- DMSO- 1H), 7.46 (br d, J =8.30 Hz, 1H), 6.95-7.04 (m, 2H), O s, s, 15% d₆ 5.41-5.63 (m, 2H),3.95-4.06 (m, 1H), 3.77 (br d, methanol, peak 2 J = 12.20 Hz, 1H),3.30-3.45 (m, 2H), 3.18 (br t, J = 10.19 Hz, 1H), 2.19-2.35 (m, 1H) 231500 MHz 7.86 (s, 1H), 7.65 (d, J = 8.04 Hz, 1H), 7.55 (d, B PhenomenexLux d₄- J = 7.79 Hz, 1H), 7.42 (t, J = 7.66 Hz, 1H), 7.16-7.26Cellulose- MeOH (m, 2H), 6.64 (br dd, J = 1.82, 9.08 Hz, 1H), 6.27 (br2, 30% t, J = 8.69 Hz, 1H), 4.89-5.03 (m, 1H), 4.13-4.24 (m, MeOH Peak 11H), 3.92-4.01 (m, 1H), 3.79-3.90 (m, 1H), 3.50- 3.64 (m, 2H), 3.39-3.48(m, 1H), 3.24-3.30 (m, 1H), 2.97-3.08 (m, 1H), 2.70 (qd, J = 9.45, 13.43Hz, 1H), 2.52 (dt, J = 4.67, 7.79 Hz, 1H), 2.17-2.34 (m, 1H) 232 500 MHz7.86 (s, 1H), 7.64 (d, J = 8.04 Hz, 1H), 7.54 (d, B Phenomenex d₄- J =7.78 Hz, 1H), 7.40 (t, J = 7.79 Hz, 1H), 7.14-7.22 Lux Cellulose- MeOH(m, 2H), 6.65 (br d, J = 7.53 Hz, 1H), 6.27 (br t, 2, 30% MeOH J = 9.08Hz, 1H), 4.88-5.00 (m, 1H), 4.08-4.16 (m, Peak 2 1H), 3.86-3.99 (m, 2H),3.39-3.58 (m, 3H), 3.24- 3.30 (m, 1H), 3.01-3.11 (m, 1H), 2.62-2.77 (m,1H), 2.44-2.56 (m, 1H), 2.10-2.27 (m, 1H) 233 500 MHz 8.90 (d, J = 1.30Hz, 1H), 8.82 (d, J = 1.30 Hz, 1H), B Chiralpak d₄- 7.46 (d, J = 8.56Hz, 1H), 7.28 (d, J = 2.08 Hz, 1H), IC, 15% MeOH 7.18 (dd, J = 1.95,8.43 Hz, 1H), 5.65 (s, 2H), 3.38- MeOH, Peak 1 3.51 (m, 2H), 3.28 (br d,J = 3.37 Hz, 1H), 3.16-3.25 (m, 1H), 3.08-3.15 (m, 1H), 2.23-2.36 (m,1H), 2.07-2.22 (m, 1H) 234 500 MHz 8.91 (d, J = 1.30 Hz, 1H), 8.82 (d, J= 1.04 Hz, 1H), B Chiralpak d₄- 7.50 (d, J = 1.82 Hz, 1H), 7.15-7.19 (m,1H), 7.09- IC, 15% MeOH 7.15 (m, 1H), 5.67 (s, 2H), 3.42.-3.55 (m, 2H),3.33- MeOH, Peak 2 3.38 (m, 1H), 3.20-3.28 (m, 1H), 3.13-3.20 (m, 1H),2.25-2.38 (m, 1H), 2.09-2.23 (m, 1H) 235 600 MHz 8.30 (br d, J = 7.79Hz, 1H), 7.46 (dd, J = 7.47, 11.21 — — d₆- Hz, 1H), 7.36 (dd, J = 7.32,10.74 Hz, 1H), 4.64 (s, DMSO 2H), 4.30-4.46 (m, 1H), 3.84-3.93 (m, 1H),3.37- 3.43 (m, 1H), 2.93-3.05 (m, 2H), 2.79 (dd, J = 8.72, 12.46 Hz,1H), 2.06-2.17 (m, 1H), 1.75-1.85 (m, 1H) 1.10 (dd, J = 1.87, 6.54 Hz,6H) 236 600 MHz 7.46 (dd, J = 7.47, 11.21 Hz, 1H), 7.38 (dd, J = 7.32, —— d₆- 10.74 Hz, 1H), 4.73 (s, 2H), 4.33-4.47 (m, 1H), 4.27 DMSO (dt, J =4.67, 7.63 Hz, 2H), 3.89-3.99 (m, 2H), 3.34- 3.40 (m, 2H), 2.95-3.06 (m,2H), 2.80 (dd, J = 8.25, 12.61 Hz, 1H), 2.26-2.34 (m, 2H), 2.06-2.18 (m,1H), 1.75-1.85 (m, 1H) 237 600 MHz 7.44-7.52 (m, 1H), 7.28-7.38 (m, 1H),5.02-5.12 (m, — — d₆- 2H), 4.32-4.47 (m, 1H), 3.55-3.86 (m, 2H), 3.18-DMSO 3.55 (m, 5H), 2.93-3.07 (m, 2H), 2.74-2.84 (m, 1H), 2.03-2.17 (m,1H), 1.71-1.84 (m, 1H), 1.01-1.36 (m, 6H) (mixture of 2diastereomers/rotamers) 238 600 MHz 7.53 (dd, J = 7.47, 11.21 Hz, 1H),7.09-7.20 (m, 1H), — — d₆- 5.28 (t, J = 9.96 Hz, 1H), 4.30-4.48 (m, 1H),3.56- DMSO 3.64 (m, 1H), 3.42-3.50 (m, 1H), 3.30-3.42 (m, 2H), 2.97-3.09(m, 2H), 2.88 (s, 3H), 2.76-2.85 (m, 1H), 2.54-2.59 (m, 1H), 2.27-2.37(m, 1H), 2.07-2.19 (m, 1H), 1.76-1.93 (m, 1H) 239 600 MHz 7.45-7.54 (m,2H), 7.39-7.44 (m, 2H), 7.35-7.38 (m, — — d₆- 2H), 7.27 (dt, J = 0.93,7.32 Hz, 1H), 5.21-5.32 (m, DMSO 1H), 4.32-4.50 (m, 1H), 4.08-4.20 (m,1H), 3.61- 3.68 (m, 1H), 3.29-3.39 (m, 2H), 2.97-3.11 (m, 2H), 2.73-2.90(m, 1H), 2.51-2.63 (m, 1H), 2.07-2.32 (m, 4H), 1.82-1.92 (m, 1H) 240600MHz 7.76-7.81 (m, 2H), 7.53-7.58 (m, 1H), 7.48-7.53 (m, — — d₆- 2H),7.34-7.41 (m, 1H), 5.59 (dd, J = 9.65, 11.21 Hz, DMSO 1H), 4.34-4.49 (m,1H), 4.06 (br t, J = 9.19 Hz, 1H), 3.92-4.00 (m, 1H), 3.34-3.43 (m, 2H),3.01-3.09 (m, 2H), 2.82 (ddd, J = 8.88, 12.69, 14.87 Hz, 1H), 2.64- 2.72(m, 1H), 2.54-2.61 (m, 1H), 2.10-2.20 (m, 1H), 1.80-1.90 (m, 1H) 241 500MHz 8.51 (s, 2H), 7.95 (d, J = 0.78 Hz, 1H), 7.65-7.70 (m, B Chiralceld₄- 1H), 7.59-7.64 (m, 1H), 5.57-5.68 (m, 2H), 4.77- OJ-H, 15% MeOH 4.95(m, 1H), 4.23-4.32 (m, 1H), 3.98-4.06 (m, 1H), MeOH Peak 2 3.95 (s, 3H),3.71-3.80 (m, 1H), 3.42-3.53 (m, 2H), 2.34-2.44 (m, 1H), 2.01-2.15 (m,1H) 242 500 MHz 8.52 (s, 2H), 7.94 (s, 1H), 7.66-7.74 (m, 2H), 5.54- BChiralcel d₄- 5.67 (m, 2H), 4.77-4.93 (m, 1H), 4.21-4.30 (m, 1H), OJ-H,15% MeOH 4.01 (br d, J = 12.98 Hz, 1H), 3.96 (s, 3H), 3.71-3.78 MeOHPeak 1 (m, 1H), 3.43-3.50 (m, 2H), 2.32-2.46 (m, 1H), 1.98-2.14 (m, 1H)243 600 MHz 8.82 (br d, J = 3.89 Hz, 3H), 8.73 (s, 1H), 7.94 (d, BChiralpak d₆- J = 1.04 Hz, 1H), 7.86-7.90 (m, 1H), 7.80-7.85 (m, AD-H,20% DMSO 1H), 7.64-7.68 (m, 1H), 7.56-7.63 (m, 1H), 5.58- MeOH Peak 15.72 (m, 2H), 4.87-5.04 (m, 1H), 3.94-4.03 (m, 1H), 3.57-3.64 (m, 2H),3.31 (dd, J = 10.12, 12.98 Hz, 1H), 3.16 (br t, J = 11.42 Hz, 1H),2.20-2.32 (m, 1H), 1.79-1.96 (m, 1H) 244 600 MHz 8.73 (br d, J = 4.15Hz, 3H), 8.71 (d, J = 1.56 Hz, 1H), B Chiralpak d₆- 8.01 (d, J = 1.30Hz, 1H), 7.83-7.91 (m, 1H), 7.79 AD-H, 20% DMSO (dd, J = 1.43, 8.17 Hz,1H), 7.51-7.60 (m, 1H), 7.37- MeOH Peak 2 7.51 (m, 1H), 5.55-5.73 (m,2H), 4.81-5.03 (m, 1H), 3.85-3.96 (m, 1H), 3.58-3.66 (m, 1H), 3.49-3.54(m, 1H), 3.25 (dd, J = 9.86, 12.98 Hz, 1H), 3.11 (br t, J = 11.42 Hz,1H), 2.20-2.31 (m, 1H), 1.82-1.95 (m, 1H) 245 500 MHz 7.36 (dd, J =7.27, 10.64 Hz, 1H), 7.06 (dd, J = 7.01, F Chiralpak d₄- 10.12 Hz, 1H),5.39 (t, J = 9.99 Hz, 1H), 4.34-4.52 IC, 25% MeOH, MeOH (m, 1H),3.67-3.74 (m, 1H), 3.57-3.65 (m, 1H), 3.48 w/0.2% (br dd, J = 3.76, 7.14Hz, 2H), 3.08-3.20 (m, 2H), DEA Peak 1 3.01 (s, 3H), 2.95 (dd, J = 8.95,12.33 Hz, 1H), 2.64- 2.74 (m, 1H), 2.46 (qd, J = 9.81, 12.88 Hz, 1H),2.18- 2.29 (m, 1H), 1.92-2.03 (m, 1H) 246 500 MHz 7.36 (dd, J = 7.27,10.64 Hz, 1H), 7.06 (dd, J = 7.01, F Chiralpak d₄- 10.12 Hz, 1H), 5.39(t, J = 9.99 Hz, 1H), 4.36-4.52 IC, 25% MeOH, MeOH (m, 1H), 3.67-3.74(m, 1H), 3.58-3.65 (m, 1H), w/0.2% 3.52-3.58 (m, 1H), 3.38-3.46 (m, 1H),3.11-3.20 (m, DEA Peak 2 2H), 3.01 (s, 3H), 2.93 (dd, J = 8.56, 12.46Hz, 1H), 2.61-2.71 (m, 1H), 2.45 (qd, J = 9.74, 13.07 Hz, 1H), 2.18-2.29(m, 1H), 1.92-2.04 (m, 1H) 247 500 MHz 7.78 (d, J = 9.08 Hz, 2H), 7.46(d, J = 9.08 Hz, 2H), F Chiralcel d₄- 7.40 (dd, J = 7.27, 10.64 Hz, 1H),7.21 (br dd, OD-H, 30% MeOH, MeOH J = 6.88, 10.25 Hz, 1H), 5.63 (dd, J =9.47, 11.03 Hz, w/0.2% 1H), 4.37-4.55 (m, 1H), 4.06-4.20 (m, 2H), 3.55-DEA Peak 1 3.63 (m, 1H), 3.41-3.49 (m, 1H), 3.14-3.23 (m, 2H), 2.96 (dd,J = 8.82, 12.20 Hz, 1H), 2.75-2.84 (m, 1H), 2.58-2.73 (m, 1H), 2.19-2.33(m, 1H), 1.92-2.06 (m, 1H) 248 500 MHz 7.77 (d, J = 8.82 Hz, 2H),7.43-7.49 (m, 2H), 7.40 F Chiralcel OD- d₄- (dd, J = 7.27, 10.64 Hz,1H), 7.17-7.24 (m, 1H), H, 30% MeOH 5.59-5.67 (m, 1H), 4.37-4.54 (m,1H), 4.06-4.20 (m, MeOH, 2H), 3.48-3.56 (m, 2H), 3.12-3.21 (m, 2H),2.95- w/0.2% DEA 3.07 (m, 1H), 2.78-2.87 (m, 1H), 2.62-2.72 (m, 1H),Peak 2 2.20-2.31 (m, 1H), 1.94-2.06 (m, 1H) 249 DMSO- 9.09 (d, J = 1.48Hz, 1H), 8.96 (d, J = 1.40 Hz, 1H), B SFC: d₆ 7.78 (d, J = 1.48 Hz, 1H),7.56 (d, J = 8.29 Hz, 1H), Chiralpak 7.50 (d, J = 8.50 Hz, 1H),5.66-5.76 (m, 2H), 4.39- AD-H, 30% 4.37 (m, 1H), 3.39-3.49 (m, 2H),3.06-3.17 (m, 1H), methanol. 2.80-2.95 (m, 2H), 2.00-2.14 (m, 2H),1.67-1.83 (m, 1H) 250 DMSO- 9.08 (d, J = 1.40 Hz, 1H), 8.97 (d, J = 1.40Hz, 1H), B SFC: d₆ 7.93 (d, J = 1.48 Hz, 1H), 7.46 (d, J = 8.36 Hz, 1H),Chiralpak 7.39 (d, J = 8.21 Hz, 1H), 5.67-5.76 (m, 2H), 4.38- AD-IL 25%4.34 (m, 1H), 3.37-3.46 (m, 2H), 3.02-3.12 (m, 1H), methanol 2.79-2.98(m, 2H), 2.00-2.16 (m, 1H), 1.68-1.79 (m, 1H) 251 DMSO- 9.10 (d, J =1.40 Hz, 1H), 8.97 (d, J = 1.32 Hz, 1H), B SFC: d₆ 7.17 (dd, J = 2.18,9.26 Hz, 1H), 6.89 (t, J = 10.46 Hz, Chiralpak 1H), 5.63-5.70 (m, 2H),4.26-4.31 (m, 1H), 3.37- AD-H, 30% 3.51 (m, 2H), 3.03-3.12 (m, 1H),2.92-3.01 (m, 1H), methanol 2.79-2.91 (m, 1H), 1.99-2.17 (m, 1H),1.70-1.84 (m, 1H) 252 DMSO- 9.02-9.15 (m, 1H), 8.93-8.98 (m, 1H), 7.17(d, B SFC: d₆ J = 8.96 Hz, 1H), 6.82-6.94 (m, 1H), 5.61-5.70 (m,Chiralpak 2H), 4.34 (dt, J = 4.28, 8.25 Hz, 1H), 3.37-3.44 (m, AD-H, 25%1H), 3.03-3.10 (m, 1H), 2.87-2.886 (m, 2H), 2.32- methanol 2.47 (m, 1H),2.02-2.18 (m, 1H), 1.69-1.83 (m, 1H) 253 DMSO- 10.99-11.51 (m, 1H),8.46-8.48 (m, 1H), 7.65-7.72 — — d₆ (m, 1H), 7.51-7.57 (m, 1H),7.13-7.20 (m, 2H), 6.84-6.95 (m, 2H), 4.09-4.26 (m, 1H), 3.88-4.08 (m,1H), 3.74-3.82 (m, 2H), 2.80-3.00 (m, 2H), 2.58- 2.67 (m, 1H), 2.20-2.26(m, 3H), 1.93-2.00 (m, 1H), 1.74-1.84 (m, 1H), 1.47-1.55 (m, 2H) 254DMSO- 8.48-8.64 (s, 1H), 7.83-7.99 (m, 1H), 7.43-7.58 (m, — — d₆ 1H),7.26 (d, J = 8.30 Hz, 1H), 7.01-7.20 (m, 2H), 6.89 (br dd, J = 3.05,5.51 Hz, 2H), 4.55 (s, 1H), 4.01 (br d, J = 12.20 Hz, 1H), 3.74-3.83 (m,1H), 3.55- 3.69 (m, 1H), 2.82-3.04 (m, 2H), 2.58-2.66 (m, 1H), 2.35-2.47(m, 1H), 2.25 (s, 2H), 1.95 (br s, 1H), 1.80 (br dd, J = 3.18, 6.16 Hz,1H), 1.44-1.63 (m, 1H), 255 DMSO- 9.04 (d, J = 2.02 Hz, 1H), 8.30 (d, J= 8.16 Hz, 1H), B SFC: d₆ 7.40-7.47 (m, 2H), 7.05 (t, J = 7.59 Hz, 1H),6.92- Chiralpak 7.00 (m, 2H), 5.81-5.87 (m, 1H), 3.37-3.48 (m, 1H), IC,25% 2.85-2.94 (m, 2H), 2.52-2.69 (m, 3H), 2.37-2.47 (m, methanol 1H),2.15 (s, 3H), 1.85-1.95 (m, 2H), 1.71-1.82 (m, 1H), 1.59-1.69 (m, 1H),1.14-1.26 (m, 1H) 256 DMSO- 9.04 (d, J = 1.48 Hz, 1H), 8.29 (d, J = 8.18Hz, 1H), B SFC: d₆ 7.45 (d, J = 8.80 Hz, 1H), 7.41 (d, J = 8.07 Hz, 1H),Chiralpak 7.05 (ddd, J = 1.87, 6.46, 8.02 Hz, 1H), 6.90-7.00 (m, IC, 25%2H), 5.80-5.88 (m, 1H), methanol 3.38-3.50 (m, 2H), 3.21-3.28 (m, 1H),2.82-2.94 (m, 1H), 2.67 (dd, J = 9.07, 11.64 Hz, 1H), 2.51-2.62 (m, 2H),2.25 (s, 2H), 2.15 (s, 1H), 1.91 (d, J = 7.16 Hz, 4H), 1.62-1.80 (m,2H), 1.18-1.28 (m, 1H) 257 DMSO- 8.92 (s, 2H), 7.15 (dd, J = 2.18, 9.34Hz, 1H), 6.86 B SFC/MS with d₆ (t, J = 10.48 Hz, 1H), 5.51-5.60 (m, 2H),4.298-4.44 MeOH as co- (m, 1H), 3.34-3.42 (m, 2H), 3.02-3.10 (m, 1H),solvent at 10% 2.88-2.97 (m, 1H), 2.81 (dd, J = 8.45, 12.57 Hz, 1H),iso-cratic 2.04-2.12 (m, 1H), 1.66-1.82 (m, 1H) Column: 4- Ethylpyridine21.2 × 150 mm 258 DMSO- 8.92 (s, 2H), 7.06 (dd, J = 2.26, 8.88 Hz, 1H),6.95 B SFC/MS with d₆ (dt, J = 2.18, 10.63 Hz, 1H), 5.50-5.57 (m, 2H),4.26- MeOH as co- 4.43 (m, 1H), 3.25-3.42 (m, 1H), 2.93-3.09 (m, 2H),solvent at 10% 2.86 (br s, 1H), 2.76 (br dd, J = 8.60, 12.34 Hz, 1H),iso-cratic 2.00-2.09 (m, 1H), 1.62-1.73 (m, 1H) Column: 4- Ethylpyridine21.2 × 150 mm 259 DMSO- 7.85 (d, J = 0.78 Hz, 1H), 7.57 (d, J = 8.49 Hz,1H), — — d₆ 7.50 (dd, J = 7.43, 11.17 Hz, 1H), 7.33 (dd, J = 7.08, 8.41Hz, 1H), 7.25 (dd, J = 7.32, 10.67 Hz, 1H), 6.77 (d, J = 6.70 Hz, 1H),5.59-5.66 (m, 2H), 4.27-4.41 (m, 1H), 4.03 (s, 3H), 3.42-3.59 (m, 1H),2.99-3.12 (m, 1H), 2.89-2.98 (m, 1H), 2.83 (dd, J = 8.68, 12.57 Hz, 1H),2.29-2.47 (m, 1H), 1.94-2.11 (m, 1H), 1.67-1.77 (m, 1H) 260 DMSO- 8.97(dd, J = 1.56, 4.20 Hz, 1H), 8.61 (d, J = 8.02 Hz, — — d₆ 1H), 7.97 (d,J = 8.49 Hz, 1H), 7.67 (t, J = 7.95 Hz, 1H), 7.61-7.65 (m, 1H), 7.53(dd, J = 7.47, 11.13 Hz, 1H), 7.25 (dd, J = 7.32, 10.67 Hz, 1H), 7.00(d, J = 7.19 Hz, 1H), 5.79-5.86 (m, 2H), 4.27-4.40 (m, 1H), 3.37-3.52(m, 2H), 3.01-3.10 (m, 1H), 2.89-2.99 (m, 1H), 2.83 (dd, J = 8.49, 12.53Hz, 1H), 2.02 (dddd, J = 4.28, 8.60, 12.62, 16.77 Hz, 1H), 1.67-1.83 (m,1H) 261 DMSO- 8.91 (dd, J = 1.71, 4.13 Hz, 1H), 8.40 (dd, J = 1.48, BSFC: d₆ 8.25 Hz, 1H), 7.98 (d, J = 8.10 Hz, 1H), 7.87 (d, Chiralpak J =7.16 Hz, 1H), 7.65 (t, J = 7.71 Hz, 1H), 7.57 (dd, IC column, 20% J =4.17, 8.21 Hz, 1H), 7.37-7.52 (m, 2H), 6.75 (q, methanol. J = 7.19 Hz,1H), 4.33-4.41 (m, 1H), 3.35-3.46 (m, 2H), 2.96-3.09 (m, 2H), 2.72 (dd,J = 8.76, 12.34 Hz, 1H), 2.52-2.56 (m, 1H), 1.97-2.10 (m, 4H), 1.63-1.79 (m, 1H) 262 DMSO- 8.91 (dd, J = 1.71, 4.13 Hz, 1H), 8.39 (dd, J =1.56, B SFC: d₆ 8.25 Hz, 1H), 7.98 (d, J = 8.02 Hz, 1H), 7.86 (d,Chiralpak J = 7.16 Hz, 1H), 7.65 (t, J = 7.71 Hz, 1H), 7.56 (dd, ICcolumn, 20% J = 4.13, 8.25 Hz, 1H), 7.46 (dd, J = 7.63, 11.13 Hz,methanol. 1H), 7.39 (dd, J = 7.36, 11.25 Hz, 1H), 6.73 (q, J = 7.14 Hz,1H), 4.28-4.36 (m, 1H), 3.36-3.46 (m, 1H), 3.14-3.28 (m, 2H), 2.83-2.97(m, 2H), 2.52- 2.55 (m, 1H), 2.38 (br s, 1H), 1.91-2.05 (m, 4H),1.68-1.85 (m, 1H) 263 DMSO- 7.92 (t, J = 1.71 Hz, 1H), 7.84 (td, J =1.31, 7.65 Hz, — — d₆ 1H), 7.51-7.59 (m, 4H), 7.14 (s, 1H), 5.57 (s,2H), 4.29-4.50 (m, 1H), 3.36-3.49 (m, 3H), 2.99-3.13 (m, 1H), 2.87 (dd,J = 8.37, 12.57 Hz, 1H), 2.04-2.20 (m, 1H). 1.77-1.92 (m, 1H) 264 DMSO-8.06 (s, 1H), 7.68 (d, J = 8.02 Hz, 1H), 7.54 (t, — — d₆ J = 9.20 Hz,1H), 7.18 (dd, J = 7.59, 10.47 Hz, 1H), 6.99 (t, J = 7.59 Hz, 1H), 6.48(d, J = 7.30 Hz, 1H), 5.98 (d, J = 17.36 Hz, 1H), 5.91 (d, J = 17.36 Hz,1H), 4.36-4.45 (m, 1H), 4.31-4.35 (m, 3H), 3.40-3.57 (m, 2H), 3.08-3.13(m, 1H), 2.90-2.97 (m, 1H), 2.86 (dd, J = 8.14, 12.57 Hz, 1H), 2.54-2.66(m, 1H), 1.99-2.07 (m, 1H), 1.67-1.83 (m, 1H) 265 DMSO- 7.47-7.56 (m,3H), 7.42 (dd, J = 7.67, 8.52 Hz, 1H), — — d₆ 6.75 (dd, J = 7.24, 10.82Hz, 1H), 5.50-5.56 (m, 2H), 4.29-4.47 (m, 1H), 3.40-3.51 (m, 1H),3.35-3.40 (m, 1H), 3.01-3.14 (m, 1H), 2.91-3.01 (m, 1H), 2.82 (dd, J =8.76, 12.42 Hz, 1H), 2.08-2.17 (m, 1H), 1.72-1.84 (m, 1H) 266 DMSO-7.37-7.41 (m, 1H), 7.18 (d, J = 7.38 Hz, 1H), 7.07 (t, — — d₆ J = 6.39Hz, 2H), 4.62-4.71 (m, 2H), 4.25 (t, J = 7.63 Hz, 2H), 3.89-3.97 (m,2H), 3.40-3.48 (m, 1H), 3.23-3.29 (m, 1H), 2.83-2.91 (m, 1H), 2.52-2.65(m, 1H), 2.25-2.32 (m, 1H), 1.83- 1.93 (m, 1H), 1.71-1.79 (m, 1H),1.60-1.69 (m, 1H), 1.21-1.33 (m, 1H) 267 DMSO- 9.53 (br s, 1H), 8.97 (d,J = 1.63 Hz, 1H), 8.33 (d, B SFC: d₆ J = 8.66 Hz, 1H), 7.55 (d, J = 8.47Hz, 1H), 7.23 (dd, Chiralpak IC, J = 2.22, 9.07 Hz, 1H), 6.88 (t, J =10.52 Hz, 1H), 15% methanol 5.82-5.96 (m, 1H), 4.02 (br dd, J = 3.93,7.90 Hz, (initial 2H), purification). 3.61-3.79 (m, 1H), 3.57 (br s,1H), 3.50 (br dd, Chiralpak AD- J = 4.09, 12.42 Hz, 1H), 3.28 (br s,1H), 3.13-3.26 H, 10% (m, 1H), 3.09 (br d, J = 12.77 Hz, 1H), 2.51-2.66(m, methanol 2H), 1.97 (br s, 2H), 1.84-1.93 (m, 3H) (reprocess offraction A). - 268 DMSO- 9.46 (br s, 1H), 8.93-9.04 (m, 1H), 8.33 (d, J= 8.76 B SFC: d₆ Hz, 1H), 7.55 (d, J = 8.51 Hz, 1H), 7.23 (dd, J = 2.18,Chiralpak IC, 9.03 Hz, 1H), 6.89 (t, J = 10.51 Hz, 1H), 5.85-5.96 15%methanol (m, 1H), 3.92-4.07 (m, 2H), 3.83 (br s, 2H), 3.55- (initial3.79 (m, 1H), 3.50 (br dd, J = 4.13, 12.46 Hz, 1H), purification).3.25-3.33 (m, 1H), 3.13-3.25 (m, 1H), 3.09 (br d, Chiralpak AD- J =12.53 Hz, 1H), 2.51-2.56 (m, 2H), 1.96 (br s, H, 10% 2H), 1.83-1.92 (m,3H) methanol (reprocess of fraction A). 269 DMSO- 9.44 (br s, 1H),8.94-8.99 (m, 1H), 8.30-8.35 (m, B SFC: d₆ 1H), 7.49-7.56 (m, 1H), 7.23(dd, J = 2.26, 9.03 Hz, Chiralpak IC, 1H), 6.89 (t, J = 10.49 Hz, 1H),5.86-5.94 (m, 1H), 15% methanol 3.95-4.09 (m, 2H), 3.71-3.80 (m, 2H),3.57-3.69 (m, (initial 1H), 3.50 (br dd, J = 4.09, 12.26 Hz, 1H),3.12-3.26 purification). - (m, 2H), 3.09 (br d, J = 12.77 Hz, 1H),2.51-2.62 (m, Lux-Cellulose 2H), 1.91-1.97 (m, 1H), 1.85-1.91 (m, 3H) 2,15% methanol (reprocess of fraction B). - 270 DMSO- 9.45 (br s, 1H),8.97 (d, J = 1.48 Hz, 1H), 8.29-8.36 B SFC: d₆ (m, 1H), 7.48-7.56 (m,1H), 7.23 (dd, J = 2.18, 9.03 Chiralpak IC, Hz, 1H), 6.89 (t, J = 10.48Hz, 1H), 5.85-5.94 (m, 15% methanol 1H), 3.97-4.07 (m, 2H), 3.71-3.80(m, 2H), 3.57- (initial 3.69 (m, 1H), 3.29 (br s, 1H), 3.12-3.26 (m,1H), purification). - 3.09 (br d, J = 12.53 Hz, 1H), 2.52-2.55 (m, 2H),Lux-Cellulose 1.96-2.06 (m, 1H), 1.94 (br s, 1H), 1.83-1.91 (m, 2, 15%3H) methanol (reprocess of fraction B). 271 DMSO- 9.32 (br s, 1H), 8.86(br s, 1H), 8.32-8.37 (m, 1H), B SFC: d₆ 7.55-7.59 (m, 1H), 6.99 (dt, J= 2.06, 10.53 Hz, 1H), Chiralpak IC, 6.79 (dd, J = 1.99, 8.99 Hz, 1H),5.92 (q, J = 7.16 Hz, 15% methanol 1H), 3.95-4.10 (m, 2H), 3.81 (br d, J= 9.50 Hz, 1H), (initial 3.70-3.78 (m, 1H), .61-3.69 (m, 1H), 3.39-3.48purification). - (m, 2H), 3.07-3.17 (m, 1H), 2.52-2.55 (m, 2H),Chiralcel OZ- 1.87-1.99 (m, 5H) H, 25% methanol (reprocess of fractionC). - 272 DMSO- 9.33 (br s, 1H), 8.88 (br s, 1H), 8.35 (br d, J = 8.17 BSFC: d₆ Hz, 1H), 7.57 (d, J = 8.25 Hz, 1H), 6.97-7.10 (m, Chiralpak IC,1H), 6.79 (br d, J = 8.88 Hz, 1H), 5.89-5.98 (m, 1H), 15% methanol3.99-4.07 (m, 2H), 3.78-3.84 (m, 1H), 3.70-3.78 (m, (initial 1H), 3.64(br t, J = 11.29 Hz, 1H), 3.41-3.53 (m, purification). - 1H), 3.24 (brs, 1H), 3.07-3.17 (m, 1H), 2.54 (s, fraction C). 2H), 1.86-1.99 (m, 5H)Regis Whelk- O s, s, 20% methanol (reprocess of peaks C1-C3). 273 DMSO-9.33 (br s, 1H), 8.90 (br d, J = 18.92 Hz, 1H), 8.32- B SFC: d₆ 8.37 (m,1H), 7.57 (dd, J = 6.89, 7.67 Hz, 1H), 6.99 Chiralpak IC, (t, J = 10.22Hz, 1H), 6.79 (br d, J = 8.95 Hz, 1H), 15% methanol 5.87-5.94 (m, 1H),3.97-4.09 (m, 2H), 3.81 (br d, (initial J = 8.95 Hz, 1H), 3.70-3.78 (m,1H), 3.61-3.69 (m, purification). - 1H), 3.57-3.69 (m, 1H), 3.29 (br s,1H), 3.15 (br d, Regis Whelk- J = 14.09 Hz, 1H), 2.52-2.56 (m, 2H), 2.00(br d, O s, s, 30% J = 5.99 Hz, 1H), 1.92 (d, J = 7.16 Hz, 4H) methanol(reprocess of fraction D). 274 DMSO- 9.33 (br s, 1H), 8.80-8.96 (m, 1H),8.32-8.37 (m, B SFC: d₆ 1H), 7.57 (t, J = 7.49 Hz, 1H), 6.99 (dt, J =2.02, 10.51 Chiralpak IC, Hz, 1H), 6.79 (br d, J = 9.03 Hz, 1H),5.87-5.94 (m, 15% methanol 1H), 3.96-4.08 (m, 2H), 3.80 (br s, 1H),3.70-3.78 (initial (m, 1H), 3.55-3.69 (m, 1H), 3.40-3.53 (m, 1H), 3.15purification). - (br d, J = 14.17 Hz, 1H), 3.10 (br d, J = 13.39 Hz,1H), Regis Whelk- 2.51-2.55 (m, 2H), 1.92 (d, J = 7.16 Hz, 5H) O s, s,30% methanol (reprocess of fraction D). 275 DMSO- 8.27 (br d, J = 7.21Hz, 1H), 7.47 (dd, J = 7.47, 11.21 — — d₆ Hz, 1H), 7.34 (dd, J = 7.32,10.67 Hz, 1H), 4.62-4.69 (m, 2H), 4.32-4.44 (m, 2H), 3.33-3.50 (m, 1H),3.17 (br s, 1H), 2.96-3.11 (m, 2H), 2.77-2.85 (m, 1H), 2.66 (d, J = 4.59Hz, 3H), 2.07-2.15 (m, 1H), 1.75- 1.83 (m, 1H) 276 DMSO- 7.46 (t, J =9.25 Hz, 1H), 7.40 (t, J = 8.98 Hz, 1H), — — d₆ 4.98-5.07 (m, 2H),4.35-4.47 (m, 1H), 3.63-3.73 (m, 2H), 3.56-3.62 (m, 4H), 3.38-3.54 (m,2H), 3.22-3.37 (m, 2H), 3.17 (br s, 1H), 2.94-3.10 (m, 1H), 2.80 (dd, J= 8.14, 12.57 Hz, 1H), 2.06-2.17 (m, 1H), 1.75-1.84 (m, 1H) 277 DMSO-7.46 (dd, J = 7.47, 11.13 Hz, 1H), 7.38 (dd, J = 7.32, — — d₆ 10.74 Hz,1H), 4.84-4.94 (m, 2H), 4.35-4.44 (m, 1H), 3.51-3.66 (m, 2H), 3.23-3.41(m, 2H), 2.94- 3.11 (m, 4H), 2.80 (dd, J = 8.21, 12.57 Hz, 2H), 2.29-2.47 (m, 1H), 2.02-2.18 (m, 2H), 1.96 (quin, J = 6.83 Hz, 1H), 1.75-1.86(m, 1H) 278 DMSO- 7.46 (dd, J = 7.47, 11.21 Hz, 1H), 7.37 (dd, J = 7.36,— — d₆ 10.78 Hz, 1H), 4.93-5.02 (m, 2H), 4.32-4.44 (m, 1H), 3.24-3.42(m, 1H), 3.17 (br s, 1H), 3.11 (s, 6H), 2.94-3.06 (m, 1H), 2.88 (s, 1H),2.79 (dd, J = 8.21, 12.65 Hz, 1H), 2.05-2.16 (m, 1H), 1.74- 1.84 (m, 1H)279 DMSO- 7.53 (dd, J = 7.55, 11.13 Hz, 1H), 7.39 (dd, J = 7.43, B SFC:d₆ 11.09 Hz, 1H), 5.51 (q, J = 6.98 Hz, 1H), 4.39-4.47 Chiralpak IC (dt,J = 4.13, 7.94 Hz, 1H), 3.07-3.26 (m, 3H), 2.72- analytical 2.81 (m,7H), 2.52-2.56 (m, 1H), 2.10-2.28 (m, 1H), column, 15% 1.71-1.86 (m,1H), 1.61 (d, J = 7.01 Hz, 3H) methanol with 0.2% DEA 280 DMSO 7.53 (dd,J = 7.55, 11.13 Hz, 1H), 7.39 (dd, J = 7.43, B SFC: d₆ 11.09 Hz, 1H),5.51 (q, J = 6.98 Hz, 1H), 4.39-4.47 Chiralpak IC (dt, J = 4.13, 7.94Hz, 1H), 3.07-3.26 (m, 3H), 2.72- analytical 2.81 (m, 7H), 2.52-2.56 (m,1H), 2.10-2.28 (m, 1H), column, 15% 1.71-1.86 (m, 1H), 1.61 (d, J = 7.01Hz, 3H) methanol with 0.2% DEA 281 DMSO- 7.46 (dd, J = 7.47, 11.21 Hz,1H), 7.37 (dd, J = 7.36, — — d₆ 10.78 Hz, 1H), 4.99 (d, J = 2.34 Hz,2H), 4.31-4.39 (m, 1H), 3.40-3.54 (m, 3H), 3.19-3.29 (m, 1H), 2.93-3.04(m, 2H), 2.78 (dd, J = 8.25, 12.53 Hz, 1H), 2.06-2.16 (m, 1H), 1.71-1.83(m, 3H), 1.54-1.66 (m, 4H), 1.40-1.53 (m, 2H) 282 DMSO- 8.31-8.41 (m,1H), 7.47 (dd, J = 7.47, 11.21 Hz, 1H), — — d₆ 7.35 (dd, J = 7.28, 10.70Hz, 1H), 4.61-4.68 (m, 2H), 4.32-4.47 (m, 1H), 3.35-3.45 (m, 1H),3.11-3.28 (m, 2H), 2.95-3.08 (m, 2H), 2.80 (dd, J = 8.68, 12.65 Hz, 1H),2.03-2.18 (m, 1H), 1.99 (br s, 1H), 1.56-1.91 (m, 1H), 1.06 (t, J = 7.24Hz, 3H) 283 DMSO- 8.94 (s, 2H), 7.80 (d, J = 1.09 Hz, 1H), 7.55 (d, BSFC: d₆ J = 8.39 Hz, 1H), 7.50 (d, J = 8.39 Hz, 1H), 5.54-5.62 ChiralpakAD- (m, 2H), 4.44-4.57 (m, 1H), H analytical 3.45-3.56 (m, 2H),3.07-3.13 (m, 1H), 2.81 (dd, column, 30% J = 8.56, 12.92 Hz, 1H),2.52-2.64 (m, 1H), 2.17 (s, methanol 3H), 1.95-2.10 (m, 1H), 1.70-1.82(m, 1H) 284 DMSO- 8.94 (s, 2H), 7.91 (d, J = 1.01 Hz, 1H), 7.46 (dd, BSFC: d₆ J = 1.56, 8.25 Hz, 1H), 7.39 (d, J = 8.25 Hz, 1H), 5.60Chiralpak AD- (s, 2H), 4.42-4.57 (m, 1H), 3.47-3.54 (m, 1H), 3.37- Hanalytical 3.46 (m, 1H), 3.04-3.11 (m, 1H), 2.79 (dd, J = 8.52, column,30% 12.81 Hz, 1H), 2.52-2.65 (m, 1H), 2.18 (s, 3H), methanol 1.95-2.11(m, 1H), 1.71-1.84 (m, 1H) 285 DMSO- 7.42 (d, J = 8.49 Hz, 1H), 7.38 (d,J = 2.02 Hz, 1H), B SFC: d₆ 7.12-7.15 (m, 1H), 4.73-4.80 (m, 2H),4.57-4.69 Chiralpak IC (m, 1H), 3.95 (t, J = 7.71 Hz, 2H), 3.51-3.56 (m,1H), analytical 3.31-3.44 (m, 2H), 3.28 (br s, 1H), 3.17 (s, 1H),column, 45% 2.99-3.10 (m, 1H), 2.95 (br dd, J = 9.34, 12.61 Hz,methanol. 1H), 2.25-2.32 (m, 2H), 2.06-2.23 (m, 1H), 1.72- 1.89 (m, 1H)286 DMSO- 7.47 (d, J = 1.95 Hz, 1H), 7.25 (d, J = 8.49 Hz, 1H), B SFC:d₆ 7.13 (dd, J = 1.95, 8.49 Hz, 1H), 4.72-4.79 (m, 2H), Chiralpak IC4.58-4.70 (dt, J = 4.59, 8.68 Hz, 1H), 4.23-4.29 (m, analytical 1H),3.94 (t, J = 7.71 Hz, 1H), 3.51-3.59 (m, 1H), column, 45% 3.31-3.47 (m,2H), 3.28 (br s, 1H), 3.17 (s, 1H), methanol. 3.01-3.12 (m, 1H), 2.96(br dd, J = 9.23, 12.65 Hz, 2H), 2.13-2.31 (m, 1H), 1.79-1.89 (m, 1H)287 DMSO- 7.77 (d, J = 1.01 Hz, 1H), 7.46-7.54 (m, 2H), 4.74- B SFC: d₆4.86 (m, 3H), 4.25-4.36 (m, 2H), 3.96 (t, J = 7.71 Hz, Chiralpak IC 2H),3.12-3.29 (m, 3H), 3.01-3.09 (m, 2H), 2.30 analytical (quin, J = 7.69Hz, 2H), 2.01-2.08 (m, 1H), 1.80-1.99 column, 35% (m, 1H) methanol 288DMSO- 7.86-7.92 (m, 1H), 7.46-7.52 (m, 1H), 7.33-7.42, (m, B SFC: d₆1H), 4.74-4.86 (m, 3H), 4.25-4.36 (m, 2H), 3.96 (t, Chiralpak IC J =7.71 Hz, 2H), 3.12-3.29 (m, 3H), 3.01-3.09 (m, analytical 2H), 2.30(quin, J = 7.69 Hz, 2H), 2.01-2.08 (m, 1H), column, 35% 1.80-1.99 (m,1H) methanol 289 DMSO- 8.92 (s, 2H), 7.42 (dd, J = 4.87, 8.68 Hz, 1H),7.11 B SFC: d₆ (dd, J = 2.49, 9.26 Hz, 1H), 6.92 (ddd, J = 2.57, 8.68,Chiralcel 10.08 Hz, 1H), 5.47-5.56 (m, 2H), 4.26-4.42 (m, OD-H, 15% 1H),3.35-3.49 (m, 2H), 2.93-3.03 (m, 1H), 2.82- isopropanol 2.92 (m, 1H),2.74 (dd, J = 8.60, 12.42 Hz, 1H), 1.97- 2.12 (m, 1H), 1.64-1.82 (m, 1H)290 DMSO 8.92 (s, 2H), 7.24 (dd, J = 2.45, 9.77 Hz, 1H), 7.14 B SFC: d₆(dd, J = 4.75, 8.72 Hz, 1H), 6.87 (ddd, J = 2.49, 8.70, Chiralcel 9.91Hz, 1H), 5.51 (d, J = 2.10 Hz, 2H), 4.27-4.34 (m, OD-H, 15% 1H),3.35-3.44 (m, 2H), 2.98-3.06 (m, 1H), 2.83- isopropanol 2.93 (m, 1H),2.78 (dd, J = 8.60, 12.57 Hz, 1H), 1.99- 2.09 (m, 1H), 1.64-1.79 (m, 1H)291 500 MHz 8.96 (s, 1H), 8.28 (br dd, J = 1.95, 8.17 Hz, 1H), — — DMSO-7.36-7.50 (m, 1H), 7.32 (br d, J = 8.04 Hz, 1H), 7.05- d₆ 7.20 (m, 2H),6.98-7.05 (m, 1H), 5.47 (s, 2H), 3.3 (m, 1H), 2.83 (br t, J = 10.06 Hz,2H), 2.74 (br s, 1H), 2.60-2.67 (m, 1H), 1.79 (br d, J = 8.30 Hz, 1H),1.66 (br s, 1H), 1.51 (br d, J = 10.77 Hz, 1H), 1.15 (br d, J = 10.64Hz, 1H) 292 500 MHz 8.67 (d, J = 1.66 Hz, 1H), 8.02 (br d, J = 7.98 Hz,3H), — — DMSO- 7.77 (dd, J = 1.97, 8.09 Hz, 1H), 7.52 (d, J = 7.77 Hz,d₆ 1H), 7.13-7.28 (m, 3H), 5.54 (s, 2H), 3.57-3.65 (m, 1H), 3.45 (br s,1H), 3.30 (br d, J = 12.75 Hz, 1H), 3.18 (dd, J = 8.50, 12.44 Hz, 1H),2.98-3.07 (m, 1H), 1.99 (br d, J = 9.02 Hz, 1H), 1.83 (br s, 1H),1.54-1.70 (m, 2H) 293 500 MHz 9.23 (s, 1H), 8.48 (br d, J = 5.71 Hz,1H), 7.95 (br d, — — DMSO- J = 8.17 Hz, 1H), 7.88 (s, 1H), 7.79 (br d, J= 5.58 Hz, d₆ 1H), 7.57 (br d, J = 8.43 Hz, 1H), 7.44 (br d, J = 7.66Hz, 1H), 7.17 (br d, J = 7.91 Hz, 1H), 7.08 (br t, J = 7.46 Hz, 1H),6.97-7.04 (m, 1H), 5.49 (s, 2H), 2.78-2.95 (m, 2H), 2.53-2.72 (m, 2H),1.82 (br d, J = 10.25 Hz, 2H), 1.68 (br s, 1H), 1.61 (br s, 1H), 1.18(br d, J = 9.73 Hz, 1H) 294 500 MHz 8.05 (s, 1H), 7.67 (br d, J = 7.92Hz, 1H), 7.46 (br d, — — DMSO- J = 7.78 Hz, 1H), 7.08 (br t, J = 6.75Hz, 1H), 6.92- d₆ 7.03 (m, 3H), 6.59 (br d, J = 6.88 Hz, 1H), 5.83-5.96(m, 2H), 4.32 (s, 3H), 3.37-3.59 (m, 1H), 2.86-2.99 (m, 1H), 2.82 (br s,1H), 2.53-2.76 (m, 1H), 1.78 (br s, 2H), 1.65 (br s, 1H), 1.58 (br s,1H), 1.19 (br d, J = 9.99 Hz, 1H) 295 500 MHz 9.03 (s, 1H), 8.29 (br d,J = 6.74 Hz, 1H), 7.36-7.51 B SFC: DMSO- (m, 2H), 6.99-7.12 (m, 1H),6.94 (d, J = 3.94 Hz, Chiralpak d₆ 2H), 5.82-5.99 (m, 1H), 4.03 (q, J =7.15 Hz, 1H), IC, 20% methanol 3.39 (br d, J = 10.78 Hz, 1H), 3.17 (brd, J = 12.65 Hz, w/0.2% DEA 1H), 2.81-3.05 (m, 2H), 1.75-1.95 (m, 4H),1.54- 1.70 (m, 1H), 1.31-1.47 (m, 1H), 1.17 (t, J = 7.10 Hz, 1H) 296 500MHz 9.04 (d, J = 1.55 Hz, 1H), 8.24-8.31 (m, 1H), 7.36- B SFC: DMSO-7.48 (m, 2H), 7.01-7.09 (m, 1H), 6.89-6.99 (m, 2H), Chiralpak d₆5.83-5.96 (m, 1H), 3.35-3.53 (m, 2H), 3.21 (br d, IC, 20% methanol J =12.13 Hz, 1H), 3.12 (br s, 1H), 2.77-3.02 (m, w/0.2% DEA 2H), 1.75-1.95(m, 1H), 1.67 (br d, J = 9.23 Hz, 1H), 1.29-1.46 (m, 1H). 297 500 MHz9.03 (d, J = 1.55 Hz, 1H), 8.80 (br s, 3H), 8.36 (dd, B SFC: DMSO- J =2.07, 8.29 Hz, 1H), 7.66 (br d, J = 8.29 Hz, 1H), Chiralpak d₆ 7.56 (d,J = 7.98 Hz, 1H), 7.39 (br s, 1H), 7.00-7.15 IC, 20% methanol (m, 2H),6.04 (q, J = 6.77 Hz, 1H), 4.92-5.05 (m, w/0.2% DEA 1H), 3.84 (br d, J =12.75 Hz, 1H), 3.75 (br s, 1H), 3.62-3.71 (m, 1H), 3.32-3.54 (m, 1H),3.06-3.30 (m, 1H), 2.77-3.05 (m, 1H), 2.53-2.75 (m, 1H), 2.27- 2.47 (m,1H), 1.91-2.02 (m, 4H). 298 500 MHz 9.02 (d, J = 1.45 Hz, 1H), 8.80 (brs, 3H), 8.35 (dd, B SFC: DMSO- J = 2.18, 8.29 Hz, 1H), 7.63 (d, J = 7.56Hz, 1H), 7.58 Chiralpak d₆ (d, J = 7.48 Hz, 1H), 7.20-7.29 (m, 1H),7.03-7.15 IC, 20% methanol (m, 2H), 6.01 (q, J = 6.91 Hz, 1H), 4.90-5.02(m, w/0.2% DEA 1H), 3.91 (s, 1H), 3.87 (br s, 1H), 3.65-3.81 (m, 1H),3.59-3.64 (m, 1H), 3.26 (br t, J = 11.25 Hz, 1H), 2.32 (br d, J = 3.84Hz, 1H), 2.01 (d, J = 7.05 Hz, 4H) 299 500 MHz 9.07 (d, J = 1.55 Hz,1H), 8.36-8.52 (m, 4H), 7.84 (d, B SFC: DMSO- J = 8.19 Hz, 1H), 7.63 (d,J = 7.98 Hz, 1H), 7.28-7.39 Chiralpak d₆ (m, 1H), 7.21 (br d, J = 3.63Hz, 2H), 5.90 (br dd, IC, 25% methanol J = 4.77, 10.47 Hz, 1H), w/0.2%DEA 4.02 (br d, J = 14.10 Hz, 1H), 3.89 (br s, 1H), 3.59- 3.81 (m, 1H),3.33-3.54 (m, 2H), 3.10-3.32 (m, 2H), 2.56 (br dd, J = 7.20, 13.73 Hz,1H), 2.31 (qd, J = 7.03, 10.63 Hz, 1H), 2.08 (br s, 1H), 1.96-2.05 (m,1H), 1.74 (br d, J = 8.60 Hz, 1H), 1.60 (br d, J = 4.35 Hz, 1H), 0.59(br t, J = 7.15 Hz, 3H) 300 500 MHz 9.06 (d, J = 1.56 Hz, 1H), 8.51 (brs, 3H), 8.38-8.48 B SFC: DMSO- (m, 1H), 7.79 (br d, J = 8.40 Hz, 1H),7.61 (d, J = 8.09 Chiralpak d₆ Hz, 1H), 7.26-7.34 (m, 1H), 7.13-7.22 (m,2H), 5.71 IC, 25% methanol (br dd, J = 5.65, 9.80 Hz, 1H), 3.67-3.78 (m,1H), w/0.2% DEA 3.42-3.50 (m, 1H), 3.16 (s, 1H), 3.10 (br s, 1H),2.55-2.69 (m, 1H), 2.26-2.45 (m, 2H), 1.98-2.12 (m, 1H), 1.86 (br s,2H), 1.65 (br s, 1H), 1.10-1.31 (m, 1H), 0.64-0.71 (m, 3H). 301 500 MHz8.87 (s, 2H), 8.40 (br s, 2H), 7.53 (dd, J = 7.43, 11.02 — — DMSO- Hz,1H), 7.39 (t, J = 8.98 Hz, 1H), 5.50-5.60 (m, 2H), d₆ 4.72-4.84 (m, 1H),3.62-3.75 (m, 1H), 3.42-3.59 (m, 1H), 3.17-3.29 (m, 1H), 2.95-3.08 (m,2H), 2.13- 2.20 (m, 1H), 1.73-1.82 (m, 1H) 302 500 MHz 7.85 (s, 1H),7.77 (d, J = 7.71 Hz, 1H), 7.49-7.56 (m, — — DMSO- 2H), 7.44 (d, J =8.32 Hz, 1H), 7.20 (t, J = 8.97 Hz, d₆ 1H), 5.83 (q, J = 7.08 Hz, 1H),4.36-4.46 (m, 1H), 4.03-4.16 (m, 1H), 3.35-3.39 (m, 1H), 3.14-3.19 (m,1H), 2.99-3.13 (m, 1H), 2.78-2.92 (m, 1H), 2.08- 2.20 (m, 1H), 1.76-1.94(m, 4H) 303 500 MHz 8.88 (s, 2H), 7.50 (dd, J = 7.43, 11.09 Hz, 1H),7.38 — — DMSO- (t, J = 8.94 Hz, 1H), 5.49-5.58 (m, 2H), 4.45-4.54 d₆(dt, J = 4.55, 8.66 Hz, 1H), 3.43-3.61 (m, 1H), 3.38- 3.42 (m, 1H),3.05-3.24 (m, 1H), 2.95-3.03 (m, 1H), 2.86 (dd, J = 9.19, 12.61 Hz, 1H),1.98-2.11 (m, 1H), 1.66-1.76 (m, 1H) 304 500 MHz 8.50 (d, J = 2.88 Hz,1H), 7.73 (dt, J = 2.96, 8.72 Hz, — — DMSO- 1H), 7.48 (dd, J = 7.47,11.21 Hz, 1H), 7.30-7.38 (m, d₆ 2H), 5.36-5.43 (m, 2H), 4.65-4.82 (m,1H), 63.16- 3.29 (m, 2H), 3.04-3.14 (m, 1H), 2.88-3.00 (m, 2H),1.94-2.01 (m, 1H), 1.80-1.92 (m, 1H). 305 500 MHz 8.88 (s, 2H), 7.65 (s,1H), 7.58 (d, J = 8.43 Hz, 1H), B SFC: DMSO- 7.41 (dd, J = 1.25, 8.33Hz, 1H), 5.59-5.67 (m, 2H), Chiralpak d₆ 4.66-4.73 (m, 1H), 3.24-3.30(m, 2H), 3.07-3.18 AD-H, 25% (m, 1H), 2.83-2.99 (m, 2H), 1.92-2.00 (m,1H), methanol 1.75-1.90 (m, 1H). 306 500 MHz 8.88 (s, 2H), 7.75 (s, 1H),7.36 (s, 2H), 5.55-5.64 B SFC: DMSO- (m, 2H), 4.70-4.76-4.81 (m, 1H),3.24-3.31 (m, Chiralpak d₆ 2H), 3.08-3.18 (m, 1H), 2.86-3.00 (m, 2H),1.93- AD-H, 25% 2.03 (m, 1H), 1.76-1.92 (m, 1H). methanol 307 500 MHz8.46-8.51 (m, 1H), 7.74 (t, J = 8.73 Hz, 1H), 7.51 (t, — — DMSO- J =9.21 Hz, 1H), 7.41 (d, J = 8.81 Hz, 1H), 7.34 (t, d₆ J = 9.19 Hz, 1H),5.40-5.47 (m, 2H), 3.50 (br d, J = 12.46 Hz, 1H), 3.15-3.23 (m, 1H),3.10 (td, J = 4.45, 16.87 Hz, 1H), 2.97-3.02 (m, 1H), 2.52- 2.59 (m,1H), 2.18-2.29 (m, 1H), 1.98-2.11 (m, 1H). 308 500 MHz 7.63 (s, 1H),7.56 (d, J = 8.25 Hz, 1H), 7.41 (dd, B SFC: DMSO- J = 1.28, 8.29 Hz,1H), 4.76-4.89 (m, 3H), 4.26-4.33 Chiralpak d₆ (m, 2H), 3.96 (t, J =7.75 Hz, 2H), 3.15-3.29 (m, 2H), IC, 15% 2.97-3.13 (m, 2H), 2.30 (td, J= 7.66, 15.43 Hz, 2H), methanol. 1.90-2.09 (m, 1H) 309 500 MHz 7.73 (s,1H), 7.41 (s, 2H), 4.75-4.88 (m, 3H), 4.24- B SFC: DMSO- 4.34 (m, 2H),3.95 (t, J = 7.71 Hz, 2H), 3.14-3.28 (m, Chiralpak d₆ 3H), 2.98-3.12 (m,2H), 2.29 (td, J = 7.69, 15.45 Hz, IC, 15% 2H), 1.91-2.09 (m, 2H)methanol. 310 500 MHz 7.45 (dd, J = 7.47, 11.13 Hz, 1H), 7.37 (dd, J =7.32, — — DMSO- 10.74 Hz, 1H), 4.77-4.86 (m, 2H), 4.32-4.46 (m, d₆ 1H),3.59-3.67 (m, 2H), 2.94-3.12 (m, 2H), 2.78 (dd, J = 8.29, 12.57 Hz, 1H),2.00-2.13 (m, 1H), 1.84-1.94 (m, 3H), 1.71-1.84 (m, 4H), 1.35 (d, J =2.96 Hz, 6H). 311 500 MHz 8.86 (s, 1H), 8.14-8.20 (m, 1H), 7.48 (br dd,J = 5.06, B Cel2, 20% MeOD 8.69 Hz, 1H), 7.43 (br d, J = 8.30 Hz, 1H),6.93-7.01 MeOH, 0.2% (m, 2H), 5.46-5.58 (m, 2H), 3.94-4.01 (m, 1H), DEA,peak 1 3.34-3.48 (m, 3H), 3.20-3.26 (m, 1H), 3.09 (br dd, J = 5.32,12.07 Hz, 1H), 1.87 (q, J = 5.71 Hz, 2H) 312 500 MHz 8.86 (s, 1H), 8.16(br dd, J = 1.95, 8.17 Hz, 1H), 7.42 B Cel2, 20% MeOD (br d, J = 8.56Hz, 1H), 7.21 (br dd, J = 2.34, 9.34 Hz, MeOH, 0.2% 1H), 7.11 (br dd, J= 4.54, 8.69 Hz, 1H), 6.86-6.94 DEA, peak 2 (m, 1H), 5.48-5.58 (m, 2H),3.95-4.06 (m, 1H), 3.35-3.52 (m, 3H), 3.11-3.20 (m, 1H), 1.81-1.92 (m,2H) 313 400 MHz 8.45 (br s, 2H), 7.89 (d, J = 8.40 Hz, 2H), 7.55-7.64 BChiralpak d₆- (m, 3H), 7.31 (t, J = 7.62 Hz, 1H), 7.18 (t, J = 7.62 Hz,IC, 30% DMSO 1H), 7.08 (d, J = 8.19 Hz, 1H), 5.98 (q, J = 6.98 Hz, IPAPeak 1 1H), 3.64-3.74 (m, 2H), 3.44-3.51 (m, 1H), 3.31- 3.38 (m, 1H),3.11-3.20 (m, 1H), 1.96-2.05 (m, 2H), 1.93 (d, J = 7.05 Hz, 3H),1.64-1.79 (m, 2H) 314 400 MHz 8.40 (br s, 3H), 7.85 (d, J = 8.50 Hz,2H), 7.55-7.61 B Chiralpak d₆- (m, 1H), 7.52 (d, J = 8.29 Hz, 2H), 7.25(br t, J = 7.62 IC, 30% DMSO Hz, 1H), 7.04-7.15 (m, 2H), 5.89 (q, J =7.05 Hz, IPA Peak 2 1H), 3.72-3.78 (m, 2H), 3.31-3.38 (m, 2H), 3.13-3.22 (m, 1H), 2.02-2.08 (m, 1H), 2.00 (d, J = 7.05 Hz, 3H), 1.89-1.97(m, 1H), 1.62-1.79 (m, 2H) 315 400 MHz 8.43 (br s, 3H), 7.97 (dd, J =1.14, 10.06 Hz, 1H), — — d₆- 7.70 (d, J = 7.59 Hz, 1H), 7.58 (d, J =7.88 Hz, 1H), DMSO 7.39-7.48 (m, 1H), 7.23-7.38 (m, 3H), 5.52-5.65 (m,2H), 3.79 (br d, J = 10.16 Hz, 1H), 3.34-3.51 (m, 3H). 3.11-3.22 (m,1H), 1.95-2.04 (m, 1H), 1.83- 1.95 (m, 1H), 1.58-1.75 (m, 2H) 316 400MHz 8.55 (br s, 3H), 7.60 (d, J = 7.77 Hz, 1H), 7.45 (d, — — d₆- J =7.92 Hz, 2H), 7.27-7.39 (m, 5H), 5.47-5.62 (m, DMSO 2H), 3.92 (br d, J =10.37 Hz, 1H), 3.64-3.74 (m, 1H), 3.41-3.53 (m, 2H), 3.18-3.29 (m, 1H),1.96- 2.05 (m, 1H), 1.86-1.96 (m, 1H), 1.57-1.76 (m, 2H) 317 400 MHz8.67 (br s, 3H), 7.87 (d, J = 8.40 Hz, 2H), 7.51-7.62 B Chiralpak d₆-(m, 3H), 7.26 (t, J = 7.00 Hz, 1H), 7.04-7.17 (m, 2H), IC, 25% DMSO5.94-6.01 (m, 1H), 5.10-5.30 (m, 1H), 3.84-3.97 (m, IPA Peak 1 1H),3.57-3.68 (m, 2H), 3.23-3.37 (m, 2H), 2.18- 2.2.9 (m, 1H), 2.07-2.18 (m,1H), 1.95 (d, J = 7.05 Hz, 3H) 318 400 MHz 8.85 (br s, 3H), 7.85 (d, J =8.40 Hz, 2H), 7.52-7.63 B Chiralpak d₆- (m, 3H), 7.22-7.35 (m, 1H),7.06-7.18 (m, 2H), 5.94 IC, 25% DMSO (q, J = 7.05 Hz, 1H), 5.13-5.34 (m,1H), 3.83-4.00 IPA Peak 2 (m, 1H), 3.72-3.80 (m, 1H), 3.51-3.61 (m, 1H),3.40 (br s, 2H), 2.24 (br d, J = 2.38 Hz, 2H), 1.99-2.05 (m, 3H) 319 400MHz 8.83 (br s, 3H), 7.87 (d, J = 8.40 Hz, 2H), 7.53-7.62 B Chiralpakd₆- (m, 3H), 7.28 (t, J = 7.06 Hz, 1H), 7.14 (t, J = 7.77 Hz, IC, 25%DMSO 1H), 7.05 (d, J = 8.09 Hz, 1H), 5.98 (q, J = 6.88 Hz, IPA Peak 11H), 4.89-5.11 (m, 1H), 3.87 (br d, J = 12.75 Hz, 1H), 3.78 (br d, J =6.84 Hz, 1H), 3.42-3.61 (m, 2H), 3.18-3.29 (m, 1H), 2.29-2.38 (m, 1H),1.98-2.07 (m, 1H), 1.95 (d, J = 6.95 Hz, 3H) 320 400 MHz 8.86 (br s,3H), 7.85 (d, J = 8.40 Hz, 2H), 7.50-7.61 B Chiralpak d₆- (m, 3H), 7.25(t, J = 7.52 Hz, 1H), 7.04-7.15 (m, 2H), IC, 25% DMSO 5.94 (q, J = 6.81Hz, 1H), 4.87-5.09 (m, 1H), 3.91 (br IPA Peak 2 d, J = 12.75 Hz, 1H),3.79 (br s, 1H), 3.47-3.55 (m, 1H), 3.35-3.44 (m, 1H), 3.22-3.31 (m,1H), 2.27- 2.38 (m, 1H), 2.02-2.08 (m, 1H), 1.99 (d, J = 7.15 Hz, 3H)321 400 MHz 8.48 (br s, 3H), 8.21 (d, J = 1.45 Hz, 1H), 7.84 (dd, — —d₆- J = 1.45, 8.09 Hz, 1H), 7.61 (d, J = 7.98 Hz, 1H), DMSO 7.31-7.45(m, 2H), 7.19-7.29 (m, 2H), 5.45-5.60 (m, 2H), 3.73-3.82 (m, 1H),3.42-3.54 (m, 2H), 3.34 (br d, J = 13.06 Hz, 1H), 3.17 (br t, J = 9.43Hz, 1H), 1.95-2.06 (m, 1H), 1.83-1.94 (m, 1H), 1.59-1.78 (m, 2H) 322 600MHz 7.91 (d, J = 8.49 Hz, 2H), 7.48-7.56 (m, 2H), 7.19 B SFC: DMSO- (dd,J = 7.32, 10.90 Hz, 1H), 5.88 (q, J = 7.06 Hz, Chiralcel d₆ 1H),4.32-4.48 (m, 1H), 3.35-3.41 (m, 1H), 3.24- OJ-H, 15% 3.28 (m, 1H),3.17-3.22 (m, 3H), 2.99-3.09 (m, 1H), methanol. 2.87 (dd, J = 8.52,12.50 Hz, 1H), 2.51-2.57 (m, 1H), 2.08-2.19 (m, 1H), 1.98 (br d, J =7.08 Hz, 1H), 1.74- 1.90 (m, 1H) 323 600 MHz 7.90 (d, J = 7.91 Hz, 2H),7.47-7.56 (m, 2H), 7.20 B SFC: DMSO- (dd, J = 7.28, 10.86 Hz, 1H), 5.88(q, J = 7.06 Hz, Chiralcel d₆ 1H), 4.32-4.41 (m, 1H), 3.36-3.43 (m, 1H),3.16- OJ-H, 15% 3.27 (m, 1H), 2.99-3.13 (m, 1H), 2,80 (dd, J = 8.56,methanol. 12.46 Hz, 1H), 2.51-2.62 (m, 1H), 2.08-2.26 (m, 1H), 1.93 (d,J = 7.16 Hz, 3H), 1.79-1.91 (m, 1H) 324 600 MHz 7.74 (d, J = 7.73 Hz,1H), 7.42-7.52 (m, 3H), 7.33- B SFC: DMSO- 7.41 (m, 2H), 5.87 (q, J =7.14 Hz, 1H), 4.31-4.42 Chiralpak d₆ (m, 1H), 3.20-3.27 (m, 1H), 3.17(s, 1H), 2.91-3.00 AD-H, 10% (m, 2H), 2.78 (dd, J = 8.88, 12.30 Hz, 1H),1.99-2.14 methanol (m, 1H), 1.94 (d, J = 7.24 Hz, 4H), 1.69-1.87 (m, 1H)325 600 MHz 7.72 (d, J = 8.01 Hz, 1H), 7.51 (dd, J = 7.67, 11.09 Hz, BSFC: DMSO- 1H), 7.41-7.46 (m, 2H), 7.32-7.40 (m, 2H), 5.87 (q, Chiralpakd₆ J = 7.11 Hz, 1H), 4.31-4.41 (m, 1H), 3.25-3.40 (m, AD-H, 10% 1H),3.17 (s, 1H), 3.11 (br d, J = 12.61 Hz, 1H), 2.92- methanol. 3.07 (m,1H), 2.74 (dd, J = 8.99, 12.34 Hz, 1H), 2.01- 2.17 (m, 1H), 1.94 (d, J =7.16 Hz, 4H), 1.71-1.89 (m, 1H) 326 600 MHz 7.52 (dd, J = 7.63, 11.06Hz, 1H), 7.33-7.39 (m, 3H), B SFC: DMSO- 7.19 (dd, J = 7.28, 10.94 Hz,1H), 7.08-7.15 (m, 1H), Chiralpak d₆ 5.74-5.82 (m, 1H), 4.34-4.45(m,1H), 3.35-3.42 (m, AD-H, 10% 1H), 2.97-3.08 (m, 2H), 2.86 (dd, J = 8.68,12.42 Hz, methanol. 1H), 2.05-2.20 (m, 1H), 1.78-1.96 (m, 5H) 327 600MHz 7.52 (dd, J = 7.59, 11.09 Hz, 1H), 7.34-7.38 (m, 3H), B SFC: DMSO-7.19 (dd, J = 7.32, 10.90 Hz, 1H), 7.08-7.16 (m, 1H), Chiralpak d₆5.73-5.82 (m, 1H), 4.35-4.45 (m, 1H), 3.34-3.43 (m, AD-H, 10% 2H),3.21-3.28 (m, 1H), 3.00-3.10 (m, 1H), 2.81 methanol. (dd, J = 8.52,12.42 Hz, 1H), 2.07-2.21 (m, 1H), 1.78-1.96 (m, 5H) 328 600 MHz 7.77 (s,1H), 7.41-7.54 (m, 4H), 5.83 (q, J = 7.14 Hz, B SFC: DMSO- 1H),4.28-4.40 (m, 1H), 3.10 (br d, J = 12.38 Hz, Chiralcel d₆ 1H), 2.90-3.04(m, 2H), 2.72 (dd, J = 8.87, 12.30 Hz, OD-H column, 10% 1H), 2.00-2.16(m, 1H), 1.95 (d, J = 7.16 Hz, 3H), isopropanol. 1.68-1.87 (m, 2H) 329600 MHz 7.79 (s, 1H), 7.42-7.54 (m, 4H), 5.84 (q, J = 7.14 Hz, B SFC:DMSO- 1H), 4.27-4.41 (m, 1H), 3.16-3.27 (m, 1H), 2.87- Chiralcel d₆ 3.00(m, 2H), 2.78 (dd, J = 9.03, 12.38 Hz, 1H), 2.00- OD-H column, 10% 2.13(m, 1H), 1.95 (d, J = 7.16 Hz, 3H), 1.69-1.86 isopropanol. (m, 2H) 330600 MHz 7.75-7.80 (m, 1H), 7.48 (dd, J = 7.63, 11.06 Hz, 1H), B SFC:DMSO- 7.26 (dd, J = 7.28, 11.02 Hz, 1H), 7.14-7.20 (m, 2H), 15 Chiralpakd₆ 5.89 (q, J = 6.95 Hz, 1H), 4.40-4.47 (m, 1H), 4.33- AD-H, 15% 4.39(m, 1H), 3.27-3.30 (m, 2H), 2.94-3.01 (m, 2H), isopropanol 2.86 (dd, J =8.95, 12.46 Hz, 1H), 2.02-2.14 (m, 1H), 1.85-2.00 (m, 5H) 331 600 MHz7.74-7.82 (m, 1H), 7.48 (dd, J = 7.67, 11.09 Hz, 1H), B SFC: DMSO- 7.26(dd, J = 7.32, 11.05 Hz, 1H), 7.14-7.20 (m, 2H), 15 Chiralpak d₆ 5.88(q, J = 7.11 Hz, 1H), 4.34-4.48 (m, 1H), 3.28- AD-H, 15% 3.39 (m, 1H),3.23 (br dd, J = 5.41, 7.43 Hz, 2H), isopropanol 3.03-3.13 (m, 1H), 2.78(dd, J = 8.37, 12.42 Hz, 1H), 2.07-2.22 (m, 1H), 1.94 (d, J = 7.16 Hz,3H), 1.64- 1.86 (m, 1H) 332 600 MHz 7.57 (s, 1H), 7.59 (d, J = 11.19 Hz,1H), 7.52 (dd, B SFC: DMSO- J = 7.59, 11.09 Hz, 1H), 7.26 (dd, J = 7.28,10.94 Hz, Chiralpak d₆ 1H), 7.10 (d, J = 8.54 Hz, 1H), 5.77 (q, J = 7.16Hz, AD-H 25 cm 1H), 4.32-4.45 (m, 1H), 3.24-3.38 (m, 1H), 2.96- column,20% 3.09 (m, 2H), 2.85 (dd, J = 8.56, 12.46 Hz, 1H), 2.05- isopropanol2.21 (m, 1H), 1.77-1.94 (m, 5H) 333 600 MHz 7.51-7.61 (m, 3H), 7.26 (t,J = 9.06 Hz, 1H), 7.10 (d, B SFC: DMSO- J = 8.29 Hz, 1H), 5.74-5.81 (m,1H), 4.31-4.45 (m, Chiralpak d₆ 1H), 3.21-3.28 (m, 1H), 2.98-3.12 (m,2H), 2.80 AD-H 25 cm (dd, J = 8.49, 12.46 Hz, 1H), 2.09-2.20 (m, 1H),column, 20% 1.78-1.93 (m, 5H) isopropanol 334 600 MHz 7.62 (ddd, J =3.15, 5.99, 9.15 Hz, 1H), 7.48 (dd, B SFC: DMSO- J = 7.59, 11.09 Hz,1H), 7.35 (dd, J = 7.32, 11.05 Hz, Chiralpak d₆ 1H), 7.13-7.25 (m, 2H),5.91 (q, J = 7.14 Hz, 1H), AD-H, 15% 4.32-4.44 (m, 1H), 3.25-3.29 (m,1H), 2.92-3.03 (m, isopropanol. 2H), 2.87 (dd, J = 8.84, 12.26 Hz, 1H),1.99-2.14 (m, 1H), 1.86-1.96 (m, 5H), 1.83 (br s, 1H) 335 600 MHz 7.72(d, J = 8.17 Hz, 2H), 7.53 (dd, J = 7.55, 10.90 Hz, B SFC: DMSO- 1H),7.45 (br d, J = 7.08 Hz, 2H), 7.17 (t, J = 8.84 Hz, Chiralpak d₆ 1H),5.87 (q, J = 6.95 Hz, 1H), 4.31-4.40 (m, 1H), AD-H, 15% 3.35-3.41 (m,2H), 3.21-3.26 (m, 1H), 3.17 (s, 1H), isopropanol. 2.97-3.10 (m, 2H),2.77-2.94 (m, 1H), 2.02-2.18 (m, 1H), 1.93 (d, J = 7.16 Hz, 3H),1.72-1.90 (m, 3H) 336 600 MHz 7.72 (d, J = 8.17 Hz, 2H), 7.53 (dd, J =7.55, 10.90 Hz, B SFC: DMSO- 1H), 7.45 (br d, J = 7.08 Hz, 2H), 7.17 (t,J = 8.84 Hz, Regis Whelk- d₆ 1H), 5.87 (q, J = 6.95 Hz, 1H), 4.31-4.45(m, 1H), O s, s, 15% 3.21-3.26 (m, 1H), 3.17 (s, 1H), 2.97-3.10 (m, 1H),methanol. 2.77-2.94 (m, 1H), 2.02-2.18 (m, 1H), 1.93 (d, J = 7.16 Hz,3H), 1.72-1.90 (m, 2H) 337 600 MHz 7.51 (dd, J = 7.59, 10.78 Hz, 1H),7.32-7.39 (m, 4H), B SFC: DMSO- 7.15 (dd, J = 7.32, 10.90 Hz, 1H), 5.81(q, J = 7.08 Hz, Regis Whelk- d₆ 1H), 4.34-4.45 (m, 1H), 3.22-3.39 (m,1H), 2.96- O s, s, 15% 3.12 (m, 2H), 2.77-2.94 (m, 1H), 2.07-2.19 (m,1H), methanol. 1.78-1.93 (m, 5H) 338 600 MHz 8.87 (s, 2H), 7.48 (dd, J =7.47, 11.13 Hz, 1H), 7.37 B — DMSO- (dd, J = 7.32, 10.74 Hz, 1H),5.39-5.55 (m, 2H), d₆ 4.68-4.77 (m, 1H), 3.14-3.28 (m, 1H), 3.01-3.11(m, 1H), 2.83-2.94 (m, 2H), 1.88-2.01 (m, 1H), 1.69- 1.87 (m, 1H), 1.63(br s, 1H) 339 600 MHz 8.50 (d, J = 2.88 Hz, 1H), 7.73 (dt, J = 2.96,8.72 Hz, B — DMSO- 1H), 7.48 (dd, J = 7.47, 11.21 Hz, 1H), 7.30-7.38 (m,d₆ 2H), 5.36-5.43 (m, 2H), 4.75-4.82 (m, 1H), 4.65- 4.74 (m, 1H),3.16-3.29 (m, 1H), 3.04-3.14 (m, 1H), 2.88-3.00 (m, 2H), 1.94-2.01 (m,1H), 1.80-1.92 (m, 1H), 1.59 (br s, 1H) 340 600 MHz 8.12 (d, J = 2.26Hz, 1H), 7.71 (dd, J = 2.26, 8.49 Hz, B — DMSO- 1H), 7.54 (dd, J = 7.47,11.06 Hz, 1H), 7.36 (t, d₆ J = 8.91 Hz, 1H), 6.97 (d, J = 8.56 Hz, 1H),5.45-5.54 (m, 3H), 4.36-4.43 (m, 1H), 4.28-4.35 (m, 1H), 3.27-3.35 (m,1H), 3.17 (s, 1H), 2.99-3.07 (m, 1H), 2.86-2.98 (m, 1H), 2.76 (dd, J =8.68, 12.57 Hz, 1H), 2.01-2.17 (m, 1H), 1.66-1.82 (m, 1H) 341 600 MHz8.12 (d, J = 2.26 Hz, 1H), 7.71 (dd, J = 2.26, 8.49 Hz, B — DMSO- 1H),7.54 (dd, J = 7.47, 11.06 Hz, 1H), 7.36 (t, d₆ J = 8.91 Hz, 1H), 6.97(d, J = 8.56 Hz, 1H), 5.45-5.54 (m, 2H), 4.28-4.43 (m, 1H), 3.27-3.35(m, 1H), 3.17 (s, 1H), 2,99-3.07 (m, 1H), 2,86-2.98 (m, 1H), 2.76 (dd, J= 8.68, 12.57 Hz, 1H), 2.01-2.17 (m, 1H), 1.66-1.82 (m, 1H) 342 600 MHz7.80 (s, 1H), 7.65 (dd, J = 1.44, 7.98 Hz, 1H), 7.49- B — DMSO- 7.57 (m,1H), 7.38 (s, 1H), 7.32, (dd, J = 7.24, 10.67 d₆ Hz, 1H), 6.97 (d, J =8.02 Hz, 1H), 5.33-5.40 (m, 2H), 4.29-4.42 (m, 1H), 3.36-3.45 (m, 1H),3.16-3.28 (m, 1H), 2.98-3.05 (m, 1H), 2.86-2.95 (m, 1H), 2.76 (dd, J =8.72, 12.61 Hz, 1H), 1.98-2.10 (m, 1H), 1.65-1.79 (m, 1H) 343 600 MHz7.51-7.59 (m, 2H), 7.44 (dd, J = 2.57, 8.56 Hz, 1H), B — DMSO- 7.37 (dd,J = 7.28, 10.70 Hz, 1H), 6.89 (d, J = 2.49 Hz, d₆ 1H), 5.31-5.38 (m,2H), 4.29-4.41 (m, 1H), 3.35- 3.46 (m, 1H), 3.25-3.29 (m, 1H), 2.99-3.05(m, 1H), 2.85-2.96 (m, 1H), 2.77 (dd, J = 8.64, 12.53 Hz, 1H), 1.91-2.09(m, 1H), 1.65-1.76 (m, 1H) 344 600 MHz 7.48-7.56 (m, 3H), 7.39 (dd, J =7.32, 10.67 Hz, 1H), B — DMSO- 7.24 (d, J = 8.25 Hz, 2H), 5.33-5.42 (m,2H), 4.31- d₆ 4.43 (m, 1H), 3.43 (ddd, J = 3.39, 7.07, 8.86 Hz, 1H),3.36-3.39 (m, 1H), 3.17 (d, J = 4.75 Hz, 1H), 2.92- 3.08 (m, 1H), 2.81(dd, J = 8.56, 12.61 Hz, 1H), 1.98- 2.11 (m, 1H), 1.93 (t, J = 18.84 Hz,3H), 1.63-1.87 (m, 1H) 345 600 MHz 7.74 (s, 1H), 7.52-7.60 (m, 2H), 7.22(dd, J = 7.36, B — DMSO- 10.63 Hz, 1H), 6.68 (d, J = 8.02 Hz, 1H),5.31-5.40 d₆ (m, 2H), 4.09-4.41 (m, 1H), 3.36-3.45 (m, 1H), 3.15-3.24(m, 1H), 3.00-3.07 (m, 1H), 2.87-2.98 (m, 1H), 2.78 (dd, J = 8.33, 12.61Hz, 1H), 2.34-2.39 (m, 3H), 1.98-2.10 (m, 1H), 1.61- 1.79 (m, 1H) 346600 MHz 8.16 (d, J = 1.63 Hz, 1H), 7.75 (dd, J = 1.60, 8.06 Hz, B —DMSO- 1H), 7.55 (dd, J = 7.43, 11.09 Hz, 1H), 7.37 (dd, d₆ J = 7.32,10.67 Hz, 1H), 6.89 (d, J = 8.10 Hz, 1H), 5.38-5.46 (m, 2H), 4.29-4.40(m, 1H), 3.26 (br s, 2H), 2.98-3.06 (m, 1H), 2.83-2.97 (m, 1H), 2.75(dd, J = 8.60, 12.57 Hz, 1H), 1.98-2.16 (m, 1H), 1.62-1.79 (m, 1H) 347600 MHz 8.12 (d, J = 2.26 Hz, 1H), 7.71 (dd, J = 2.26, 8.49 Hz, B —DMSO- 1H), 7.54 (dd, J = 7.44, 11.09 Hz, 1H), 7.36 (dd, d₆ J = 7.28,10.70 Hz, 1H), 6.97 (d, J = 8.56 Hz, 1H), 5.46-5.53 (m, 2H), 4.24-4.43(m, 1H), 3.09-3.24 (m, 2H), 2.99-3.06 (m, 1H), 2.83-2.98 (m, 1H), 2.76(dd, J = 8.60, 12.57 Hz, 1H), 2.02-2.10 (m, 1H), 1.67-1.86 (m, 1H) 348600 MHz 7.51 (dd, J = 7.47, 11.21 Hz, 1H), 7.35-7.42 (m, 1H), B — DMSO-7.15-7.28 (m, 4H), 6.86 (d, J = 7.65 Hz, 1H), 5.30 (s, d₆ 2H), 4.19-4.43(m, 1H), 3.37-3.49 (m, 2H), 2.98- 3.09 (m, 1H), 2.89-2.97 (m, 1H), 2.78(dd, J = 8.80, 12.61 Hz, 1H), 1.95-2.09 (m, 1H), 1.65-1.83 (m, 1H) 349600 MHz 7.44-7.52 (m, 3H), 7.36 (t, J = 8.95 Hz, 1H), 7.09 B — DMSO-(ddd, J = 2.18, 4.63, 8.52 Hz, 1H), 5.28-5.35 (m, d₆ 2H), 4.27-4.47 (m,1H), 3.38-3.47 (m, 1H), 3.09- 3.23 (m, 1H), 2.93-3.07 (m, 2H), 2.80 (dd,J = 8.60, 12.57 Hz, 1H), 2.00-2.14 (m, 1H), 1.69-1.88 (m, 1H) 350 600MHz 7.49 (dd, J = 7.43, 11.17 Hz, 1H), 7.25 (dd, J = 7.32, B — DMSO-10.67 Hz, 1H), 7.14 (d, J = 1.95 Hz, 1H), 6.93 (dd, d₆ J = 1.95, 8.17Hz, 1H), 6.71 (d, J = 8.17 Hz, 1H), 5.18 (s, 2H), 4.24-4.43 (m, 1H),3.84 (s, 3H), 3.36-3.48 (m, 1H), 3.11-3.28 (m, 1H), 2.97-3.06 (m, 1H),2.89-2.97 (m, 1H), 2.77 (dd, J = 8.80, 12.61 Hz, 1H), 1.96-2.09 (m, 1H),1.64-1.82, (m, 1H) 351 600 MHz 7.50 (dd, J = 7.47, 11.13 Hz, 1H), 7.39(dd, J = 7.24, B — DMSO- 10.74 Hz, 1H), 7.29 (t, J = 9.79 Hz, 1H),7.00-7.08 d₆ (m, 2H), 5.34 (s, 2H), 4.29-4.45 (m, 1H), 3.37-3.50 (m,2H), 2.99-3.07 (m, 1H), 2.90-2.98 (m, 1H), 2.78 (dd, J = 8.64, 12.53 Hz,1H), 2.04-2.12 (m, 1H), 1.69-1.87 (m, 1H) 352 600 MHz 7.84 (d, J = 7.55Hz, 1H), 7.51-7.61 (m, 3H), 7.30 (t, B — DMSO- J = 8.69 Hz, 1H), 6.75(d, J = 7.71 Hz, 1H), 5.45 (s, d₆ 2H), 4.22-4.39 (m, 1H), 3.34-3.42 (m,1H), 3.22- 3.28 (m, 1H), 2.95-3.09 (m, 1H), 2.83-2.92 (m, 1H), 2.62-2.78(m, 1H), 1.89-2.03 (m, 1H), 1.58-1.74 (m, 1H) 353 600 MHz 7.91 (dd, J =1.01, 7.71 Hz, 1H), 7.64 (dt, J = 1.21, B — DMSO- 7.73 Hz, 1H),7.49-7.56 (m, 2H), 7.33 (dd, J = 7.28, d₆ 10.70 Hz, 1H), 6.98 (d, J =7.86 Hz, 1H), 5.49-5.55 (m, 2H), 4.26-4.42 (m, 1H), 3.36-3.46 (m, 1H),3.09-3.26 (m, 1H), 2.99-3.07 (m, 1H), 2.86-2.96 (m, 1H), 2.77 (dd, J =8.68, 12.57 Hz, 1H), 1.92-2.09 (m, 1H), 1.64-1.82 (m, 1H) 354 600 MHz7.54 (s, 1H), 7.51-7.53 (m, 1H), 7.35 (dt, J = 1.56, B — DMSO- 7.67 Hz,1H), 7.23-7.31 (m, 2H), 6.78-6.82 (m, 1H), d₆ 5.32-5.40 (m, 2H),4.24-4.44 (m, 1H), 3.36-3.51 (m, 1H), 2.99-3.14 (m, 1H), 2.87-2.96 (m,1H), 2.77 (dd, J = 8.60, 12.57 Hz, 1H), 2.00-2.07 (m, 1H), 1.85-1.98 (m,1H), 1.65-1.78 (m, 1H) 355 600 MHz 7.50-7.57 (m, 2H), 7.29 (t, J = 9.13Hz, 1H), 7.17 (dt, B — DMSO- J = 2.65, 8.49 Hz, 1H), 6.86-6.90 (m, 1H),5.29-5.36 d₆ (m, 2H), 4.19-4.46 (m, 1H), 3.35-3.48 (m, 1H), 3.26-3.29(m, 1H), 2.99-3.14 (m, 1H), 2.87-2.95 (m, 1H), 2.77 (dd, J = 8.72, 12.61Hz, 1H), 2.01-2.09 (m, 1H), 1.63-1.79 (m, 1H) 356 600 MHz 7.76 (dd, J =2.65, 9.03 Hz, 1H), 7.57 (dd, J = 7.47, B — DMSO- 11.13 Hz, 1H), 7.46(dt, J = 2.65, 8.45 Hz, 1H), 7.33 d₆ (dd, J = 7.28, 10.63 Hz, 1H), 6.81(dd, J = 5.29, 8.64 Hz, 1H), 5.38-5.45 (m, 2H), 4.25-4.41 (m, 1H),3.34-3.49 (m, 1H), 3.23-3.29 (m, 1H), 2.95-3.01 (m, 1H), 2.83-2.91 (m,1H), 2.74 (dd, J = 8.91, 12.57 Hz, 1H), 1.97-2.04 (m, 1H), 1.62-1.80 (m,1H) 357 600 MHz 7.36-7.52 (m, 3H), 7.29 (t, J = 9.45 Hz, 1H), 6.92- B —DMSO- 6.98 (m, 1H), 5.27-5.34 (m, 2H), 4.26-4.48 (m, 1H), d₆ 3.38-3.49(m, 1H), 3.36-3.38 (m, 1H), 2.93-3.07 (m, 2H), 2.81 (dd, J = 8.60, 12.57Hz, 1H), 2.05-2.13 (m, 1H), 1.71-1.89 (m, 1H) 358 600 MHz 7.46-7.54 (m,2H), 7.39 (dd, J = 7.32, 10.67 Hz, 1H), B — DMSO- 7.24 (dd, J = 1.87,8.33 Hz, 1H), 6.96 (t, J = 8.29 Hz, d₆ 1H), 5.35 (s, 2H), 4.27-4.44 (m,1H), 3.36-3.49 (m, 2H), 3.00-3.17 (m, 1H), 2.89-2.98 (m, 1H), 2.78 (dd,J = 8.68, 12.57 Hz, 1H), 2.02-2.13 (m, 1H), 1.67-1.84 (m, 1H) 359 600MHz 7.58 (d, J = 8.33 Hz, 1H), 7.44-7.53 (m, 3H), 7.04 B — DMSO- (dd, J= 2.02, 8.33 Hz, 1H), 5.30-5.36 (m, 2H), 4.30- d₆ 4.46 (m, 1H),3.38-3.51 (m, 2H), 2.93-3.07 (m, 2H), 2.80 (dd, J = 8.64, 12.61 Hz, 1H),2.05-2.13 (m, 1H), 1.68-1.86 (m, 1H) 360 600 MHz ¹H NMR (600 MHz,DMSO-d6) δ 7.55 (t, J = 8.15 B — DMSO- Hz, 1H), 7.51 (t, J = 9.00 Hz,1H), 7.43 (t, J = 8.77 Hz, d₆ 1H), 7.26 (dd, J = 1.87, 10.20 Hz, 1H),6.94 (dd, J = 1.44, 8.29 Hz, 1H), 5.30-5.37 (m, 2H), 4.32-4.46 (m, 1H),3.38-3,52 (m, 2H), 3.00-3.08 (m, 1H), 2.92-3.00 (m, 1H), 2.80 (dd, J =8.60, 12.57 Hz, 1H), 1.96-2.13 (m, 1H), 1.69-1.87 (m, 1H) 361 600 MHz7.68-7.74 (m, J = 8.17 Hz, 2H), 7.52 (dd, J = 7.43, B — DMSO- 11.17 Hz,1H), 7.41 (dd, J = 7.32, 10.67 Hz, 1H), d₆ 7.31-7.36 (m, J = 8.02 Hz,2H), 5.40-5.47 (m, 2H), 4.31-4.45 (m, 1H), 3.39-3.53 (m, 2H), 3.00-3.07(m, 1H), 2.91-2.99 (m, 1H), 2.80 (dd, J = 8.60, 12.57 Hz, 1H), 2.03-2.11(m, 1H), 1.66-1.83 (m, 1H) 362 600 MHz 7.50 (dd, J = 7.43, 11.17 Hz,1H), 7.43 (dd, J = 7.32, B — DMSO- 10.74 Hz, 1H), 7.34 (d, J = 8.17 Hz,2H), 7.27 (d, d₆ J = 8.06 Hz, 2H), 5.32-5.40 (m, 2H), 4.23-4.50 (m, 1H),3.39-3.46 (m, 1H), 3.36 (br s, 1H), 2.99-3.11 (m, 1H), 2.91-2.99 (m,1H), 2.80 (dd, J = 8.68, 12.57 Hz, 1H), 1.99-2.12 (m, 1H), 1.65-1.81 (m,1H) 363 600 MHz 7.48-7.58 (m, 3H), 7.38 (dd, J = 7.32, 10.67 Hz, 1H), B— DMSO- 7.27 (d, J = 8.10 Hz, 2H), 7.00 (t, J = 55.86 Hz, 1H), d₆5.35-5.43 (m, 2H), 4.20-4.48 (m, 1H), 3.42 (ddd, J = 3.39, 7.08, 8.91Hz, 1H), 3.36-3.38 (m, 1H), 2.99-3.08 (m, 1H), 2.91-2.99 (m, 1H), 2.80(dd, J = 8.60, 12.57 Hz, 1H), 1.98-2.11 (m, 1H), 1.65- 1.82 (m, 1H) 364600 MHz 7.43-7.52 (m, 3H), 7.27 (br d, J = 8.17 Hz, 1H), 7.19 B — DMSO-(s, 1H), 7.11 (d, J = 7.79 Hz, 1H), 5.35-5.43 (m, 2H), d₆ 4.31-4.42 (m,1 H), 3.39-3.47 (m, 1H), 3.36-3.38 (m, 1H), 2.98-3.07 (m, 1H), 2.94(tdd, J = 4.20, 7.94, 14.40 Hz, 1H), 2.80 (dd, J = 8.68, 12.57 Hz, 1H),1.69-1.86 (m, 1H) 365 600 MHz ¹H NMR (600 MHz, DMSO-d₆) δ 7.65 (d, J =8.23 B — DMSO- Hz, 1H), 7.62, (s, 1H), 7.46-7.57 (m, 3H), 7.34 (d, d₆ J= 7.71 Hz, 1H), 5.39-5.47 (m, 2H), 4.20-4.48 (m, 1H), 3.39-3.47 (m, 1H),3.35-3.38 (m, 1H), 2.91- 3.06 (m, 2H), 2.80 (dd, J = 8.68, 12.57 Hz,1H), 1.98- 2.11 (m, 1H), 1.69-1.85 (m, H) 366 600 MHz 7.76 (d, J = 7.71Hz, 1H), 7.70 (s, 1H), 7.48-7.57 (m, B — DMSO- 2H), 7.44 (t, J = 8.87Hz, 1H), 7.40 (d, J = 8.08 Hz, d₆ 1H), 5.34-5.42 (m, 2H), 4.27-4.50 (m,1H), 3.38- 3.48 (m, 1H), 3.15-3.26 (m, 1H), 3.00-3.13 (m, 1H), 2.91-3.00(m, 1H), 2.80 (dd, J = 8.60, 12.57 Hz, 1H), 1.99-2.16 (m, 1H), 1.72-1.87(m, 1H) 367 600 MHz 7.50 (dd, J = 7.43, 11.17 Hz, 1H), 7.43 (dd, J =7.32, B — DMSO- 10.74 Hz, 1H), 7.35 (s, 1H), 7.35 (d, J = 5.66 Hz, d₆1H), 7.27 (s, 1H), 7.01-7.06 (m, 1H), 5.30-5.37 (m, 2H), 4.26-4.51 (m,1H), 3.39-3.49 (m, 1H), 3.36- 3.38 (m, 1H), 2.92-3.07 (m, 2H), 2.80 (dd,J = 8.64, 12.53 Hz, 1H), 1.96-2.14 (m, 1H), 1.72-1.84 (m, 1H) 368 400MHz 7.47-7.53 (m, 1H), 7.09-7.23 (m, 5H), 7.00-7.08 (m, — — d₄- 2H),5.30 (s, 2H), 3.48-3.55 (m, 1H), 3.24-3.30 (m, MeOH 1H), 2.92-3.06 (m,2H), 2.86 (dd, J = 8.81, 11.71 Hz, 1H), 1.92-2.04 (m, 1H), 1.82 (td, J =4.07, 13.42 Hz, 1H), 1.64-1.76 (m, 1H), 1.30-1.45 (m, 1H) 369 600 MHz7.98-8.03 (m, 2H), 7.44 (d, J = 7.79 Hz, 1H), 7.34 (d, — — d₆- J = 8.41Hz, 2H), 7.16-7.18 (m, 1H), 7.07-7.11 (m, DMSO 1H), 6.99-7.04 (m, 1H),5.39 (s, 2H), 2.81-2.95 (m, 2H), 2.69 (br d, J = 2.49 Hz, 1H), 1.81-1.88(m, 1H), 1.68-1.77 (m, 1H), 1.54-1.65 (m, 1H), 1.16-1.28 (m, 1H) 370 500MHz 7.89 (br d, J = 8.04 Hz, 2H), 7.44 (br d, J = 7.53 Hz, — — d₆- 1H),7.39 (br d, J = 8.04 Hz, 2H), 7.15 (br d, J = 7.79 DMSO Hz, 1H), 7.09(br t, J = 7.14 Hz, 1H), 6.99-7.05 (m, 1H), 5.41 (s, 2H), 3.40 (br d, J= 10.38 Hz, 1H), 3.25- 3.30 (m, 1H), 2.83-2.92 (m, 2H), 2.63-2.71 (m,1H), 1.82 (br dd, J = 3.37, 8.04 Hz, 1H), 1.71 (br dd, J = 4.54, 8.69Hz, 1H), 1.52-1.65 (m, 1H), 1.15-1.27 (m, 1H) 371 500 MHz 9.23 (s, 1H),8.21 (s, 1H), 7.81 (br d, J = 8.56 Hz, — — d₆- 2H), 7.43 (br d, J = 7.27Hz, 1H), 7.33 (br d, J = 8.56 DMSO Hz, 2H), 7.19 (br d, J = 7.53 Hz,1H), 6.99-7.12 (m, 2H), 5.35 (s, 2H), 3.43 (br d, J = 9.86 Hz, 1H),2.83- 2.95 (m, 2H), 2.61-2.71 (m, 1H), 1.81-1.91 (m, 1H), 1.72 (br dd, J= 3.63, 9.08 Hz, 1H), 1.56-1.65 (m, 1H), 1.15-1.30 (m, 1H) 372 500 MHz7.90 (br d, J = 7.01 Hz, 1H), 7.62 (br t, J = 7.27 Hz, — — d₆- 1H),7.42-7.53 (m, 2H), 7.10 (br dd, J = 4.80, 7.14 DMSO Hz, 2H), 7.00-7.06(m, 1H), 6.97 (br d, J = 7.78 Hz, 1H), 5.48 (s, 2H), 3.30-3.43 (m, 2H),2.76-2.91 (m, 3H), 2.61 (br dd, J = 9.08, 11.68 Hz, 1H), 1.77-1.87 (m,1H), 1.65-1.74 (m, 1H), 1.52-1.62 (m, 1H) 373 500 MHz 7.48 (br d, J =8.04 Hz, 2H), 7.38 (br d, J = 8.04 Hz, — — d₆- 2H), 6.98 (br t, J = 7.27Hz, 1H), 6.86 (br t, J = 7.40 DMSO Hz, 1H), 6.75 (br d, J = 8.04 Hz,1H), 5.44-5.54 (m, 2H), 3.41 (br d, J = 8.82 Hz, 2H), 2.80-2.94 (m, 2H),2.61-2.69 (m, 1H), 1.86 (br dd, J = 3.76, 8.43 Hz, 1H), 1.74-1.81 (m,1H), 1.58-1.70 (m, 1H), 1.14- 1.30 (m, 1H) 374 500 MHz 7.52 (br d, J =7.01 Hz, 1H), 7.45 (br d, J = 7.79 Hz, — — d₆- 1H), 7.32 (br t, J = 7.01Hz, 1H), 7.22-7.28 (m, 1H), DMSO 6.96-7.13 (m, 3H), 6.79 (br d, J = 6.75Hz, 1H), 5.32 (s, 2H), 2.75-2.90 (m, 3H), 2.61 (br dd, J = 9.08, 11.68Hz, 1H), 1.77-1.87 (m, 1H), 1.67 (br dd, J = 3.76, 9.21 Hz, 1H),1.47-1.61 (m, 1H), 1.10-1.26 (m, 1H) 375 500 MHz 7.70 (br d, J = 7.79Hz, 2H), 7.43 (br d, J = 7.79 Hz, — — d₆- 1H), 7.34 (br d, J = 8.04 Hz,2H), 7.14 (br d, J = 7.79 DMSO Hz, 1H), 7.08 (br t, J = 7.14 Hz, 1H),6.99-7.05 (m, 1H), 5.39 (s, 2H), 3.39 (br d, J = 9.60 Hz, 2H), 2.78-2.91 (m, 3H), 2.63 (br dd, J = 9.34, 11.68 Hz, 1H), 1.81 (br dd, J =3.89, 8.04 Hz, 1H), 1.66-1.76 (m, 1H), 1.52-1.64 (m, 1H), 1.12-1.26 (m,1H) 376 500 MHz 7.40-7.47 (m, 1H), 7.23-7.37 (m, 4H), 7.17 (br d, — —d₆- J = 8.04 Hz, 1H), 6.96-7.12 (m, 2H), 5.25-5.41 (m, DMSO 2H), 3.39(br d, J = 10.90 Hz, 2H), 2.77-2.89 (m, 2H), 2.62 (br dd, J = 9.21,11.81 Hz, 1H), 1.78-1.88 (m, 1H), 1.54-1.75 (m, 2H), 1.12-1.23 (m, 1H)377 500 MHz 7.34-7.46 (m, 3H), 7.12-7.21 (m, 3H), 6.96-7.11 (m, — — d₆-2H), 5.23-5.31 (m, 2H), 3.35-3.42 (m, 2H), 2.78- DMSO 2.90 (m, 3H),2.57-2.68 (m, 1H), 1.79-1.88 (m, 1H), 1.66-1.77 (m, 1H), 1.53-1.64 (m,1H), 1.11-1.24 (m, 1H) 378 500 MHz 7.43 (br d, J = 7.79 Hz, 1H),7.30-7.37 (m, 2H), 7.25 — — d₆- (s, 1H), 7.19 (br d, J = 7.79 Hz, 1H),6.99-7.12 (m, DMSO 3H), 5.24-5.36 (m, 2H), 3.39 (br d, J = 10.12 Hz,2H), 2.78-2.92 (m, 2H), 2.62 (br dd, J = 9.08, 11.68 Hz, 1H), 1.79-1.89(m, 1H), 1.70 (br d, J = 3.63 Hz, 1H), 1.53-1.66 (m, 1H), 1.18 (br d, J= 10.38 Hz, 1H) 379 500 MHz 7.52 (br d, J = 8.30 Hz, 1H), 7.47-7.59 (m,1H), 7.42 — — d₆- (br d, J = 7.79 Hz, 1H), 7.25 (br d, J = 7.78 Hz, 2H),DMSO 6.95-7.18 (m, 3H), 5.25-5.40 (m, 2H), 3.40 (br d, J = 11.68 Hz,2H), 2.79-2.90 (m, 2H), 2.64 (br dd, J = 9.21, 11.55 Hz, 1H), 1.92 (brt, J = 18.81 Hz, 3H), 1.82 (br dd, J = 3.37, 9.08 Hz, 1H), 1.71 (br dd,J = 4.02, 9.21 Hz, 1H), 1.60 (br s, 1H), 1.09-1.2.4 (m, 1H) 380 500 MHz7.39-7.49 (m, 3H), 7.22 (br d, J = 8.30 Hz, 2H), 7.15 — — d₆- (br d, J =7.79 Hz, 1H), 6.97-7.10 (m, 2H), 5.23-5.34 DMSO (m, 2H), 3.41 (br d, J =11.68 Hz, 2H), 2.78-2.91 (m, 2H), 2.59-2.69 (m, 1H), 1.79-1.86 (m, 1H),1.68- 1.76 (m, 1H), 1.59-1.68 (m, 6H), 1.12-1.24 (m, 1H) 381 500 MHz7.53 (br d, J = 7.78 Hz, 2H), 7.43 (br d, J = 7.53 Hz, — — d₆- 1H), 7.27(br d, J = 7.79 Hz, 2H), 6.96-7.16 (m, 4H), DMSO 5.28-5.39 (m, 2H), 3.40(br d, J = 9.86 Hz, 2H), 2.76- 2.91 (m, 3H), 2.59-2.68 (m, 1H), 1.83 (brdd, J = 3.76, 8.17 Hz, 1H), 1.70 (br dd, J = 4.41, 9.34 Hz, 1H),1.51-1.62 (m, 1H), 1.11-1.25 (m, 1H) 382 500 MHz 8.37 (br d, J = 4.41Hz, 1H), 7.76 (br d, J = 8.30 Hz, — — d₆- 2H), 7.39-7.47 (m, 1H), 7.21(br d, J = 8.04 Hz, 2H), DMSO 6.97-7.17 (m, 3H), 5.33 (s, 2H), 3.40 (brd, J = 9.08 Hz, 2H), 2.78-2.91 (m, 2H), 2.63 (br dd, J = 9.47, 11.29 Hz,1H), 1.53-1.92 (m, 3H), 1.09-1.24 (m, 1H) 383 500 MHz 7.86-7.94 (m, 1H),7.57-7.66 (m, 1H), 7.36-7.50 (m, — — d₆- 1H), 6.93-7.23 (m, 5H), 5.41(s, 2H), 2.72-2.93 (m, DMSO 3H), 2.57-2.66 (m, 1H), 1.81 (br dd, J =3.11, 4.93 Hz, 1H), 1.65-1.74 (m, 1H), 1.51-1.63 (m, 1H), 1.10-1.26 (m,1H) 384 500 MHz 7.41 (br d, J = 7.53 Hz, 1H), 7.13-7.20 (m, 3H), 6.96- —— d₆- 7.08 (m, 4H), 5.20-5.27 (m, 2H), 5.11 (s, 2H), 3.41 DMSO (br d, J= 12.20 Hz, 2H), 2.81-2.89 (m, 2H), 2.63 (br dd, J = 9.08, 11.68 Hz,1H), 1.79-1.88 (m, 1H), 1.72 (br dd, J = 3.89, 8.56 Hz, 1H), 1.61 (brdd, J = 3.89, 10.90 Hz, 1H), 1.18 (br d, J = 10.38 Hz, 1H) 385 500 MHz7.71 (br d, J = 8.30 Hz, 2H), 7.44 (br d, J = 7.78 Hz, — — d₆- 1H), 7.38(br d, J = 8.04 Hz, 2H), 7.18 (br d, J = 7.79 DMSO Hz, 1H), 6.99-7.12(m, 2H), 5.36-5.45 (m, 2H), 3.37 (br d, J = 11.68 Hz, 2H), 2.71-2.89 (m,2H), 1.76- 1.84 (m, 1H), 1.65-1.73 (m, 1H), 1.48-1.61 (m, 2H), 1.11-1.22(m, 1H) 386 500 MHz 7.41 (br d, J = 7.79 Hz, 1H), 6.96-7.16 (m, 5H),7.16 — — d₆- (br s, 1H), 5.15-5.29 (m, 2H), 3.40 (br d, J = 11.42 DMSOHz, 2H), 2.79-2.89 (m, 2H), 2.58-2.67 (m, 1H), 2.24 (s, 3H), 1.79-1.87(m, 1H), 1.69 (br d, J = 3.63 Hz, 1H), 1.54-1.65 (m, 1H), 1.13-1.22 (m,1H) 387 500 MHz 7.41 (br d, J = 7.53 Hz, 1H), 7.11-7.27 (m, 5H), 6.97- —— d₆- 7.09 (m, 2H), 5.21-5.35 (m, 2H), 3.39 (br d, J = 11.94 DMSO Hz,2H), 2.79-2.89 (m, 2H), 2.62 (br dd, J = 9.21, 11.55 Hz, 1H), 1.78-1.88(m, 1H), 1.71 (br dd, J = 3.63, 8.56 Hz, 1H), 1.54-1.65 (m, 1H),1.08-1.25 (m, 1H) 388 500 MHz 8.05 (s, 1H), 7.64-7.71 (m, 1H), 7.46 (brd, J = 7.79 — — d₆- Hz, 1H), 7.02-7.12 (m, 1H), 6.90-7.02 (m, 3H), DMSO6.56-6.64 (m, 1H), 5.90 (br d, J = 5.97 Hz, 2H), 4.32 (s, 3H), 3.40 (brd, J = 10.90 Hz, 2H), 2.89-2.96 (m, 1H), 2.78-2.86 (m, 1H), 2.70 (br dd,J = 8.69, 11.81 Hz, 1H), 1.74-1.82 (m, 1H), 1.64-1.70 (m, 1H), 1.50-1.60(m, 1H), 1.11-1.26 (m, 1H) 389 500 MHz 7.40-7.45 (m, 1H), 7.24-7.32 (m,1H), 7.16 (br d, — — d₆- J = 7.79 Hz, 1H), 6.96-7.11 (m, 3H), 5.26-5.33(m, DMSO 1H), 3.37 (br d, J = 1.56 Hz, 2H), 2.77-2.91 (m, 2H), 2.58-2.65(m, 1H), 1.80-1.87 (m, 1H), 1.67-1.76 (m, 1H), 1.52-1.64 (m, 1H),1.09-1.24 (m, 1H) 390 500 MHz 7.33-7.45 (m, 2H), 7.16-7.30 (m, 2H),7.00-7.11 (m, — — d₆- 2H), 6.95 (br s, 1H), 5.22-5.33 (m, 2H), 3.39 (brd, DMSO J = 11.16 Hz, 2H), 2.85 (br d, J = 9.611 Hz, 2H), 2.63 (br dd, J= 9.34, 11.68 Hz, 1H), 1.78-1.88 (m, 1H), 1.71 (br d, J = 3.63 Hz, 1H),1.59 (br dd, J = 2.47, 10.51 Hz, 1H), 1.12-1.24 (m, 1H) 391 500 MHz 7.53(br t, J = 7.91 Hz, 1H), 7.43 (br d, J = 7.53 Hz, — — d₆- 1H), 7.23 (brd, J = 8.82 Hz, 1H), 7.18 (br d, J = 7.78 DMSO Hz, 1H), 6.99-7.12 (m,2H), 6.94 (br d, J = 7.78 Hz, 1H), 5.25-5.34 (m, 2H), 3.38 (br d, J =11.42 Hz, 2H), 2.80-2.91 (m, 2H), 2.63 (br dd, J = 9.34, 11.68 Hz, 1H),1.78-1.88 (m, 1H), 1.67-1.77 (m, 1H), 1.60 (br s, 1H), 1.12-1.24 (m, 1H)392 500 MHz 7.92 (s, 1H), 7.84 (br d, J = 7.53 Hz, 1H), 7.49-7.59 — —d₆- (m, 2H), 7.44 (br d, J = 7.01 Hz, 1H), 7.35 (br d, DMSO J = 7.01 Hz,1H), 7.04-7.16 (m, 3H), 5.47-5.57 (m, 2H), 3.38-3.46 (m, 2H), 2.85-2.96(m, 2H), 2.69 (br dd, J = 9.08, 11.42 Hz, 1H), 1.81-1.90 (m, 1H), 1.77(br dd, J = 4.15, 8.82 Hz, 1H), 1.61-1.70 (m, 1H), 1.18-1.29 (m, 1H) 393500 MHz 7.41 (br d, J = 7.53 Hz, 1H), 7.29 (s, 1H), 7.20 (br d, — — d₆-J = 7.53 Hz, 1H), 6.99-7.12 (m, 4H), 5.17-5.25 (m, DMSO 2H), 3.80 (s,3H), 3.40 (br d, J = 9.86 Hz, 2H), 2.79- 2.91 (m, 2H), 2.62 (br dd, J =9.34, 11.68 Hz, 1H), 1.84 (br dd, J = 4.02, 8.17 Hz, 1H), 1.72 (br d, J= 3.37 Hz, 1H), 1.53-1.66 (m, 2H), 1.10-1.25 (m, 1H) 394 500 MHz 8.15(br d, J = 1.30 Hz, 1H), 7.75 (br dd, J = 1.17, 7.91 — — d₆- Hz, 1H),7.46 (br d, J = 8.04 Hz, 1H), 7.00-7.14 (m, DMSO 3H), 6.88 (br d, J =8.04 Hz, 1H), 5.33-5.44 (m, 2H), 3.15-3.24 (m, 2H), 2.74-2.89 (m, 2H),2.60 (br dd, J = 9.34, 11.42 Hz, 1H), 1.77-1.85 (m, 1H), 1.63- 1.73 (m,1H), 1.46-1.57 (m, 1H), 1.09-1.25 (m, 1H) 395 500 MHz 7.66-7.74 (m, 1H),7.42-7.48 (m, 1H), 7.31-7.38 (m, — — d₆- 1H), 7.00-7.16 (m, 3H), 6.79(br d, J = 8.30 Hz, 1H), DMSO 5.30 (s, 2H), 3.14-3.27 (m, 2H), 2.73-2.91(m, 2H), 2.60 (br dd, J = 9.21, 11.81 Hz, 1H), 1.77-1.86 (m, 1H),1.67-1.74 (m, 1H), 1.50-1.61 (m, 1H), 1.09- 1.20 (m, 1H) 396 500 MHz7.54-7.58 (m, 1H), 7.44 (br d, J = 7.27 Hz, 1H), 7.33 — — d₆- (br d, J =8.04 Hz, 1H), 6.98-7.14 (m, 3H), 6.71-6.77 DMSO (m, 1H), 5.20-5.27 (m,1H), 5.18-5.28 (m, 1H), 3.10-3.23 (m, 2H), 2.75-2.88 (m, 2H), 2.58-2.64(m, 1H), 1.79-1.84 (m, 1H), 1.64-1.71 (m, 1H), 1.51- 1.58 (m, 1H), 1.16(br dd, J = 8.04, 10.90 Hz, 1H) 397 500 MHz 8.11 (br d, J = 2.08 Hz,1H), 7.67-7.74 (m, 1H), 7.46 — — d₆- (br d, J = 8.30 Hz, 1H), 7.07-7.15(m, 2H), 7.04 (br DMSO d, J = 7.53 Hz, 1H), 6.95 (br d, J = 8.56 Hz,1H), 5.46 (s, 2H), 3.17-3.26 (m, 2H), 2.78-2.88 (m, 2H), 2.57- 2.65 (m,1H), 1.77-1.86 (m, 1H), 1.66-1.75 (m, 1H), 1.53-1.62 (m, 1H), 1.14-1.22(m, 1H) 398 400 MHz 7.69-7.76 (m, 2H), 7.50-7.56 (m, 1H), 7.46 (d, — —MeOD J = 8.09 Hz, 2H), 7.11-7.19 (m, 1H), 6.95-7.07 (m, 2H), 5.91 (q, J= 7.12 Hz, 1H), 3.43 (dd, J = 3.73, 11.61 Hz, 1H), 3.27-3.31 (m, 1H),2.95-3.08 (m, 2H), 2.87 (dd, J = 8.91, 11.61 Hz, 1H), 1.96-2.00 (m, 2H),1.95-2.01 (m, 1H), 1.86-1.94 (m, 1H), 1.69- 1.83 (m, 1H), 1.33-1.47 (m,1H) 399 400 MHz Mixture of diasteromers: 7.70-7.78 (m, 2H), 7.52 — —MeOD (d, J = 7.88 Hz, 1H), 7.45 (dd, J = 6.32, 7.98 Hz, 2H), 7.15 (dt, J= 1.24, 7.57 Hz, 1H), 6.94-7.07 (m, 2H), 5.86-5.98 (m, 1H), 3.40-3.54(m, 1H), 3.36 (s, 2H), 2.97-3.09 (m, 2H), 2.86 (ddd, J = 8.91, 11.51,16.27 Hz, 1H), 2.00 (dd, J = 7.36, 8.19 Hz, 3H), 1.68-1.92 (m, 2H),1.32-1.45 (m, 1H 400 400 MHz 8.03 (br s, 3H), 7.79 (d, J = 7.67 Hz, 1H),7.72 (s, — — d₆- 1H), 7.55-7.62 (m, 1H), 7.47-7.54 (m, 2H), 7.11- DMSO7.25 (m, 3H), 5.44 (s, 2H), 3.66 (br dd, J = 3.01, 12.54 Hz, 1H), 3.47(br d, J = 2.90 Hz, 1H), 3.25- 3.34 (m, 1H), 3.21 (dd, J = 8.50, 12.23Hz, 1H), 2.98- 3.09 (m, 1H), 1.95-2.03 (m, 1H), 1.79-1.90 (m, 1H),1.53-1.71 (m, 2H) 494 500 MHz 8.77 (s, 2H), 7.39-7.45 (m, 1H), 6.98 (dd,J = 2.34, B Chiralpak d₄- 8.82 Hz, 1H), 6.85-6.93 (m, 1H), 5.50 (s, 2H),3.90 ID, 25% IPA MeOH (td, J = 3.60, 7.07 Hz, 1H), 3.31-3.44 (m, 3H),3.22- w/0.2% DEA, 3.29 (m, 1H), 3.06-3.15 (m, 1H), 3.03 (td, J = 3.50,peak 1 7.01 Hz, 1H), 1.77-1.93 (m, 2H) 495 500 MHz 7.42-7.47 (m, 1H),7.31 (d, J = 1.82 Hz, 1H), 7.18 B Chiralpak d₄- (dd, J = 1.95, 8.43 Hz,1H), 5.08 (s, 2H), 4.38-4.55 IC, 35% MeOH, MeOH (m, 1H), 3.75-3.81 (m,2H), 3.71-3.75 (m, 2H), peak 1 3.67-3.70 (m, 2H), 3.59-3.65 (m, 2H),3.53 (br d, J = 12.46 Hz, 1H), 3.38 (s, 1H), 3.16-3.22 (m, 1H),3.07-3.15 (m, 1H), 2.97 (dd, J = 8.56, 12.46 Hz, 1H), 2.18-2.29 (m, 1H),1.89-2.01 (m, 1H) 496 500 MHz 8.77 (s, 2H), 7.15-7.19 (m, 1H), 7.10-7.14(m, 1H), B Chiralpak d₄- 6.83-6.90 (m, 1H), 5.50 (s, 2H), 3.90 (td, J =3.44, ID, 25% IPA MeOH 7.14 Hz, 1H), 3.24-3.45 (m, 4H), 3.11-3.18 (m,1H), w/0.2% DEA, 2.99-3.05 (m, 1H), 1.79-1.95 (m, 2H) peak 2 497 500 MHz7.45-7.50 (m, 1H), 7.20-7.24 (m, 1H), 7.13-7.20 (m, B Chiralpak d₄- 1H),5.08 (s, 2H), 4.41-4.58 (m, 1H), 3.75-3.81 (m, IC, 35% MeOH, MeOH 2H),3.70 (td, J = 4.57, 16.28 Hz, 4H), 3.60-3.66 (m, peak 2 2H), 3.56 (dtd,J = 1.95, 4.23, 12.42 Hz, 1H), 3.41- 3.48 (m, 1H), 3.18-3.26 (m, 1H),3.10-3.16 (m, 1H), 2.99 (dd, J = 8.69, 12.59 Hz, 1H), 2.18-2.30 (m, 1H),1.89-2.02 (m, 1H) 498 600 MHz 8.97 (s, 2H), 7.50 (dd, J = 7.59, 11.09Hz, 1H), 7.13 B Chiralpak DMSO - (dd, J = 7.36, 10.94 Hz, 1H), 5.93 (q,J = 7.19 Hz, AD-H, 25% IPA, d₆ 1H), 4.36-4.57 (m, 1H), 3.38-3.56 (m,1H), 3.22 (br peak 1 d, J = 7.24 Hz, 1H), 2.94-3.00 (m, 1H), 2.88 (dd, J= 8.76, 12.34 Hz, 1H), 2.37-2.47 (m, 1H), 2.07- 2.14 (m, 1H), 1.88 (d, J= 7.16 Hz, 4H) 499 600 MHz 8.92-8.95 (m, 1H), 8.53-8.56 (m, 1H), 8.35(dd, B Chiralpak DMSO - J = 2.10, 8.17 Hz, 1H), 8.01 (d, J = 2.10 Hz,1H), 7.60 AD-H, 25% IPA, d₆ (d, J = 8.17 Hz, 1H), 5.69 (s, 2H),4.33-4.44 (m, 1H), peak 1 3.51-3.70 (m, 1H), 3.14-3.19 (m, 1H),2.81-2.91 (m, 1H), 2.51-2.55 (m, 1H), 2.37-2.47 (m, 1H), 2.02- 2.09 (m,1H), 1.62-1.76 (m, 1H). 500 600 MHz 7.45-7.54 (m, 1H), 7.26-7.42 (m,1H), 5.01-5.18 (m, — — DMSO - 2H), 4.35-4.54 (m, 2H), 4.22 (q, J = 9.60Hz, 2H), d₆ 3.32-3.41 (m, 1H), 3.20-3.26 (m, 1H), 2.94-3.07 (m, 3H),2.81 (dd, J = 8.17, 12.59 Hz, 1H), 2.65-2.74 (m, 1H), 2.02-2.19 (m, 1H),1.77 (br d, J = 9.86 Hz, 1H) 501 600 MHz 7.57-7.62 (m, 2H), 7.51 (dd, J= 7.40, 11.13 Hz, 1H), — — DMSO - 7.32 (d, J = 3.50 Hz, 1H), 5.37-5.43(m, 2H), 4.36- d₆ 4.48 (m, 1H), 3.83 (s, 3H), 3.51 (br d, J = 13.00 Hz,1H), 3.13-3.23 (m, 2H), 2.99-3.10 (m, 1H), 2.79- 2.84 (m, 1H), 2.07-2.14(m, 1H), 1.75-1.84 (m, 1H) 502 600 MHz 8.43 (br s, 2H), 7.44 (d, J =8.51 Hz, 1H), 7.41 (s, B Chiralpak DMSO - 1H), 7.14 (dd, J = 2.06, 8.45Hz, 2H), 4.98-5.07 (m, AD-H, 25% IPA, d₆ 2H), 4.73-4.92 (m, 1H),3.65-3.72 (m, 2H), 3.34 (br peak 1 s, 1H), 2.77-3.13 (m, 6H), 2.51-2.55(m, 2H), 2.16- 2.24 (m, 1H), 1.81-1.90 (m, 1H) 503 600 MHz ¹ 7.41 (dd, J= 4.87, 8.68 Hz, 1H), 7.15 (dd, J = 2.49, B Chiralpak DMSO - 9.19 Hz,1H), 6.94 (ddd, J = 2.53, 8.64, 10.08 Hz, AD-H, 25% IPA, d₆ 1H),4.67-4.80 (m, 2H), 4.50-4.65 (m, 1H), 4.22- peak 1 4.33 (m, 2H), 3.94(t, J = 7.71 Hz, 2H), 3.39-3.57 (m, 1H), 3.23-3.39 (m, 1H), 2.96-3.10(m, 1H), 2.88 (dd, J = 8.99, 12.57 Hz, 1H), 2.52-2.55 (m, 1H), 2.29(quin, J = 7.69 Hz, 2H), 2.11-2.20 (m, 1H), 1.80-1.88 (m, 1H) 504 600MHz 7.35-7.48 (m, 2H), 4.99-5.12 (m, 2H), 4.40-4.47 (m, — — DMSO - 1H),4.30-4.39 (m, 1H), 3.90 (br d, J = 13.23 Hz, d₆ 1H), 3.15-3.30 (m, 4H),2.94-3.04 (m, 2H), 2.90 (br t, J = 11.64 Hz, 1H), 2.69-2.84 (m, 2H),2.04-2.16 (m, 1H), 1.91-2.03 (m, 1H), 1.71-1.89 (m, 1H), 1.54-1.67 (m,2H) 505 600 MHz 7.40-7.52 (m, 3H), 6.92 (dd, J = 5.14, 10.98 Hz, 1H), —— DMSO - 5.14-5.18 (m, 1H), 5.08-5.12 (m, 1H), 4.75 (s, 1H), d₆ 4.57 (s,1H), 3.78-3.89 (m, 2H), 3.20-3.29 (m, 2H), 2.93-3.03 (m, 2H), 2.75-2.83(m, 2H), 2.37-2.46 (m, 1H), 1.92-2.11 (m, 2H), 1.70-1.79 (m, 1H) 506 600MHz 7.45 (d, J = 1.87 Hz, 1H), 7.20 (d, J = 8.49 Hz, 1H), B ChiralpakDMSO - 7.08 (dd, J = 2.02, 8.49 Hz, 1H), 4.94-5.04 (m, 2H), AD-H, 25%IPA, d₆ 4.33-4.48 (m, 1H), 3.28-3.38 (m, 1H), 2.96-3.13 (m, peak 2 6H),2.88 (s, 3H), 2.76-2.85 (m, 1H), 1.99-2.16 (m, 1H), 1.74-1.87 (m, 1H)507 600 MHz 7.46 (dd, J = 7.43, 11.17 Hz, 1H), 7.39 (t, J = 8.84 Hz, — —DMSO - 1H), 5.06-5.19 (m, 1H), 4.93 (br t, J = 18.33 Hz, 1H), d₆4.06-4.13 (m, 1H), 3.80-3.93 (m, 2H), 3.49-3.60 (m, 1H), 3.36-3.48 (m,1H), 3.28-3.30 (m, 1H), 3.20- 3.28 (m, 2H), 3.17 (d, J = 5.06 Hz, 1H),2.88-3.05 (m, 2H), 2.73-2.83 (m, 1H), 2.42-2.48 (m, 1H), 2.00-2.16 (m,1H), 1.92 (br s, 1H), 1.73-1.89 (m, 1H), 1.06-1.18 (m, 3H) 508 600 MHz8.97 (s, 2H), 7.50 (dd, J = 7.59, 11.09 Hz, 1H), 7.13 B Chiralpak DMSO -(dd, J = 7.36, 10.94 Hz, 1H), 5.93 (q, J = 7.19 Hz, AD-H, 25% IPA, d₆1H), 4.36-4.57 (m, 1H), 3.38-3.56 (m, 1H), 3.22 (br peak 2 d, J = 7.24Hz, 1H), 2.94-3.00 (m, 1H), 2.88 (dd, J = 8.76, 12.34 Hz, 1H), 2.37-2.47(m, 1H), 2.07- 2.14 (m, 1H), 1.88 (d, J = 7.16 Hz, 4H) 509 600 MHz 6.73(dd, J = 2.26, 8.95 Hz, 1H), 6.56-6.64 (m, 1H), B SFC: DMSO - 5.03-5.12(m, 2H), 4.29-4.49 (m, 1H), 4.22 (q, Whelk-01, 25% d₆ J = 9.58 Hz, 2H),3.89 (s, 3H), 3.26 (s, 3H), 3.18 (br methanol Peak 2 d, J = 12.53 Hz,1H), 2.89-3.00 (m, 3H), 2.68-2.77 (m, 1H), 2.07 (ddd, J = 4.01, 8.91,13.08 Hz, 1H), 1.70-1.86 (m, 1H) 510 600 MHz 7.47 (dd, J = 7.47, 11.13Hz, 1H), 7.35 (dd, J = 7.36, — — DMSO - 10.70 Hz, 1H), 4.99 (s, 2H),4.33-4.445 (m, 1H), d₆ 3.49-3.57 (m, 2H), 3.38-3.45 (m, 1H), 3.25-3.30(m, 1H), 2.91-3.04 (m, 2H), 2.78 (dd, J = 8.64, 12.53 Hz, 1H), 2.06-2.14(m, 1H), 1.71-1.87 (m, 5H), 1.57- 1.66 (m, 4H), 1.43-1.57 (m, 4H) 511600 MHz 8.39 (d, J = 1.32 Hz, 1H), 8.13 (dd, J = 1.52, 2.61 Hz, — —DMSO - 1H), 7.89 (d, J = 2.57 Hz, 1H), 7.46 (t, J = 9.08 Hz, d₆ 1H),7.42 (t, J = 8.88 Hz, 1H), 5.04-5.14 (m, 2H), 4.34-4.35 (m, 1H),3.67-3.79 (m, 4H), 3.58-3.66 (m, 4H), 3.23-3.28 (m, 1H), 2.96-3.05 (m,2H), 2.80 (dd, J = 8.06, 12.57 Hz, 1H), 2.07-2.15 (m, 1H), 1.74-1.92 (m,2H) 512 600 MHz 7.46 (t, J = 9.16 Hz, 1H), 7.39 (t, J = 9.02 Hz, 1H), —— DMSO - 4.95-5.07 (m, 2H), 4.36-4.44 (m, 1H), 4.18 (br t, d₆ J = 11.64Hz, 1H), 3.83-3.97 (m, 1H), 3.63 (s, 2H), 3.13-3.26 (m, 3H), 2.93-3.05(m, 2H), 2.73-2.89 (m, 2H), 2.68 (tt, J = 3.97, 10.94 Hz, 1H), 2.51-2.56(m, 1H), 2.09 (br d, J = 13.16 Hz, 1H), 1.89-1.98 (m, 1H), 1.74-1.89 (m,2H), 1.60-1.70 (m, 1H), 1.40- 1.50 (m, 1H) 513 600 MHz 7.46 (dd, J =7.43, 11.02 Hz, 1H), 7.39 (dd, J = 7.55, — — DMSO - 10.35 Hz, 1H),5.07-5.18 (m, 1H), 4.93 (dd, d₆ J = 14.95, 17.28 Hz, 1H), 4.33-4.48 (m,1H), 4.09- 4.16 (br d, J = 13.00 Hz, 1H), 3.82-3.93 (m, 2H), 3.53 (dt, J= 2.37, 11.46 Hz, 1H), 3.19-3.30 (m, 2H), 2.90-3.05 (m, 2H), 2.69-2.84(m, 2H), 2.44-2.48 (m, 1H), 2.06-2.16 (m, 1H), 1.72-1.90 (m, 2H), 1.39-1.52 (m, 2H), 0.85-0.97 (m, 3H) 514 600 MHz 7.20-7.26 (m, 2H), 6.95(ddd, J = 2.49, 8.74, 9.87 Hz, B SFC: DMSO - 1H), 4.71-4.77 (m, 2H),4.63-4.55 (m, 1H), 4.23- Chiralpak d₆ 4.29 (m, 2H), 3.94 (t, J = 7.71Hz, 2H), 3.45-3.63 (m, IC, 40% 1H), 3.39-3.45 (m, 1H), 3.14-3.35 (m,1H), 2.98- methanol peak 2 3.12 (m, 1H), 2.93 (dd, J = 9.19, 12.69 Hz,1H), 2.28 (quin, J = 7.69 Hz, 2H), 2.08-2.23 (m, 1H), 1.79-1.89 (m, 1H)515 600 MHz 7.69 (d, J = 8.32 Hz, 2H), 7.48-7.65 (m, 7H), 5.67- — —DMSO - 5.99 (m, 1H), 5.17-5.57 (m, 1H), 4.36-4.51 (m, 2H), d₆ 3.86 (brs, 1H), 3.49 (br d, J = 11.99 Hz, 1H), 3.38- 3.44 (m, 1H), 2.90-3.03 (m,2H), 2.67-2.84 (m, 1H), 2.12 (br s, 1H), 1.68-1.84 (m, 1H) 516 600 MHz7.46 (dd, J = 7.47, 11.13 Hz, 1H), 7.37 (dd, J = 7.32, — — DMSO - 10.74Hz, 1H), 4.94-5.04 (m, 2H), 4.28 (br d, d₆ J = 12.85 Hz, 1H), 3.93 (brd, J = 13.23 Hz, 1H), 3.21- 3.29 (m, 2H), 3.09 (br t, J = 11.91 Hz, 1H),2.93-3.03 (m, 2H), 2.78 (dt, J = 8.41, 12.53 Hz, 1H), 2.59-2.65 (m, 1H),2.07-2.14 (m, 1H), 1.67-1.82 (m, 4H), 1.63 (br d, J = 10.98 Hz, 2H),1.10-1.18 (m, 1H), 0.90- 1.00 (m, 3H) 517 600 MHz 8.47 (d, J = 5.76 Hz,1H), 7.41 (dd, J = 4.87, 8.68 Hz, B SFC: DMSO - 1H), 7.13 (dd, J = 2.49,9.26 Hz, 1H), 6.91 (ddd, Chiralpak OD d₆ J = 2.57, 8.68, 10.08 Hz, 1H),6.85 (d, J = 5.84 Hz, analytical 1H), 5.36 (s, 2H), 4.27-4.43 (m, 1H),3.74 (s, 3H), column, 15% 3.37-3.48 (m, 2H), 2.98-3.06 (m, 1H), 2.91(tdd, isopropanol J = 4.17, 7.93, 14.39 Hz, 1H), 2.80 (dd, J = 8.64,Peak 1 12.46 Hz, 1H), 1.93-2.09 (m, 1H), 1.65-1.79 (m, 1H) 518 600 MHz7.46 (t, J = 8.90 Hz, 1H), 7.40 (t, J = 9.01 Hz, 1H), — — DMSO - 5.13(dd, J = 12.96, 17.56 Hz, 1H), 4.93 (br t, d₆ J = 16.66 Hz, 1H),4.32-4.49 (m, 1H), 4.02-4.21 (m, 1H), 3.82-3.93 (m, 2H), 3.36-3.43 (m,1H), 3.19- 3.28 (m, 3H), 2.90-3.06 (m, 3H), 2.72-2.83 (m, 2H), 2.00-2.15(m, 1H), 1.79 (br s, 1H), 1.39-1.54 (m, 1H), 0.86-0.97 (m, 3H) 519 600MHz 8.81-9.03 (m, 1H), 8.27-8.41 (m, 2H), 7.63-7.75 (m, B SFC: RegisDMSO - 1H), 7.38-7.55 (m, 1H), 5.85-5.99 (m, 2H), 4.19- Whelk-O d₆ 4.51(m, 3H), 2.83-2.95 (m, 1H), 2.63-2.78 (m, 1H), analytical 1.94-2.14 (m,1H), 1.69-1.86 (m, 1H), 1.41-1.58 (m, column, 35% 1H) isopropanol. Peak2 520 600 MHz 8.63 (br s, 2H), 7.22-7.35 (m, 2H), 7.11-7.22 (m, — —DMSO - 2H), 4.74-4.85 (m, 2H), 4.28 (t, J = 7.63 Hz, 1H), d₆ 3.94 (br t,J = 7.71 Hz, 1H), 3.43-3.78 (m, 6H), 3.04- 3.20 (m, 1H), 2.38-2.59 (m,3H), 2.21-2.32 (m, 1H), 1.81-1.98 (m, 1H) 521 600 MHz 7.34-7.51 (m, 4H),7.24 (br s, 1H), 4.91-5.16 (m, — — DMSO - 3H), 4.66 (br dd, J = 2.65,17.20 Hz, 1H), 4.32-4.48 d₆ (m, 1H), 3.84-3.90 (m, 1H), 3.17 (d, J =4.13 Hz, 1H), 2.93-3.05 (m, 2H), 2.61-2.74 (m, 1H), 2.07- 2.22 (m, 1H),1.74-1.89 (m, 2H), 1.64 (br d, J = 12.77 Hz, 2H), 1.42-1.57 (m, 2H),1.26-1.38 (m, 2H) 522 600 MHz 7.48 (dd, J = 7.51, 10.78 Hz, 1H),7.33-7.43 (m, 1H), — — DMSO - 7.04 (d, J = 2.73 Hz, 2H), 7.04 (m, 1H),5.20-5.38 d₆ (m, 1H), 4.90-5.05 (m, 2H), 4.75-4.87 (m, 1H), 4.68 (dd, J= 6.85, 15.88 Hz, 1H), 3.67 (dt, J = 8.25, 13.04 Hz, 1H), 3.38-3.52 (m,1H), 3.26 (br d, J = 5.22 Hz, 1H), 3.09-3.23 (m, 3H), 2.88-3.05 (m, 1H),2.79- 2.86 (m, 1H), 2.57-2.70 (m, 1H), 2.51-2.57 (m, 1H), 2.31-2.47 (m,2H), 1.95-2.11 (m, 1H), 1.71-1.87 (m, 1H). 523 600 MHz 7.44-7.63 (m,1H), 7.32-7.40 (m, 1H), 4.96-5.13 (m, — — DMSO - 2H), 4.24-4.50 (m, 1H),3.41 (br s, 1H), 3.21 (br s, d₆ 1H), 2.96-3.03 (m, 2H), 2.33-2.46 (m,2.H), 2.17- 2.32 (m, 1H), 2.10 (br d, J = 10.20 Hz, 1H), 1.88 (br d, J =6.85 Hz, 1H), 1.77 (br d, J = 8.49 Hz, 1H), 1.67 (br d, J = 9.81 Hz,1H), 1.62 (br s, 1H), 1.56 (br s, 2H), 1.43-1.53 (m, 1H), 1.30-1.42 (m,3H), 1.21- 1.30 (m, 2H) 1.07-1.21 (m, 2H) 0.90-1.06 (m, 1H). 524 600 MHz8.47 (d, J = 5.84 Hz, 1H), 7.23 (d, J = 9.56 Hz, 1H), B SFC: DMSO -7.18-7.21 (m, 1H), 6.83-6.89 (m, 2H), 5.32-5.40 (m, Chiralpak OD d₆ 2H),4.37-4.44 (m, 1H), 4.28-4.35 (m, 1H), 3.75 (s, analytical 3H), 3.45-3.54(m, 2H), 3.03-3.10 (m, 1H), 2.83 column, 15% (dd, J = 8.68, 12.50 Hz,1H), 2.03-2.10 (m, 1H), isopropanol 1.65-1.80 (m, 1H) 525 600 MHz7.36-7.49 (m, 2H), 5.09-5.19 (m, 2H), 4.93-5.05 (m, — — DMSO - 2H),4.36-4.44 (m, 1H), 3.61 (td, J = 8.79, 13.18 Hz, d₆ 1H), 3.37-3.49 (m,1H), 3.24-3.30 (m, 1H), 3.10- 3.24 (m, 3H), 3.07 (s, 3H), 2.93-3.05 (m,3H), 2.74- 2.83 (m, 3H), 2.18-2.34 (m, 1H), 2.05-2.15 (m, 1H), 1.73-1.91(m, 1H) 526 600 MHz 7.45-7.58 (m, 2H), 5.02-5.14 (m, 2H), 4.40-4.49 (m,— — DMSO - 1H), 4.33-4.40 (m, 1H), 3.36-3.51 (m, 1H), 3.22- d₆ 3.29 (m,3H), 3.17 (s, 1H), 2.93-3.12 (m, 4H), 2.77 (ddd, J = 4.17, 8.31, 12.59Hz, 1H), 2.34-2.47 (m, 2H), 2.08-2.17 (m, 1H), 1.74-1.92 (m, 1H), 1.06(br d, J = 8.33 Hz, 2H), 0.94-1.03 (m, 2H) 527 600 MHz 7.36-7.51 (m,2H), 4.95-5.24 (m, 2H), 4.71-4.86 (m, — — DMSO - 1H), 4.45-4.54 (m, 1H),4.32-4.38 (m, 1H), 3.45- d₆ 3.55 (m, 1H), 3.35-3.44 (m, 2H), 3.24-3.31(m, 2H), 3.09-3.22 (m, 2H), 2.92-3.04 (m, 2H), 2.73-2.81 (m, 1H),2.23-2.39 (m, 2H), 2.04-2.15 (m, 1H), 1.65- 1.92 (m, 3H), 1.25 (t, J =7.05 Hz, 2H), 1.05 (br t, J = 6.77 Hz, 1H) 528 600 MHz 7.46-7.54 (m,2H), 5.00-5.15 (m, 2H), 4.68-4.86 (m, — — DMSO - 1H), 4.23 (s, 1H),3.91-4.00 (m, 1H), 3.75 (br t, d₆ J = 5.29 Hz, 1H), 3.57-3.68 (m, 3H),3.20-3.26 (m, 2H), 2.95-3.06 (m, 2H), 2.51-2.65 (m, 1H), 2.15- 2.22 (m,1H), 1.82-1.92 (m, 1H) 529 600 MHz 7.46 (dd, J = 7.51, 11.09 Hz, 1H),7.38 (dd, J = 7.32, — — DMSO - 10.74 Hz, 1H), 4.95-5.08 (m, 2H),4.28-4.38 (m, d₆ 1H), 3.99 (br d, J = 13.31 Hz, 1H), 3.46-3.55 (m, 2H),3.24-3.30 (m, 4H), 3.11-3.23 (m, 1H), 2.93- 3.10 (m, 2H), 2.68-2.82 (m,3H), 2.11 (ddd, J = 4.48, 8.31, 12.59 Hz, 1H), 1.89 (quin, J = 6.79 Hz,2H), 1.68-1.82 (m, 5H), 1.64 (dt, J = 3.43, 12.26 Hz, 1H), 1.35-1.45 (m,1H) 530 600 MHz 7.40-7.48 (m, 1H), 7.31-7.40 (m, 1H), 4.94-5.09 (m, — —DMSO - 2H), 3.73-3.91 (m, 2H), 3.42-3.57 (m, 1H), 3.08- d₆ 3.22 (m, 3H),2.97-3.05 (m, 3H), 2.79 (tt, J = 8.44, 12.15 Hz, 2H), 2.33-2.48 (m, 1H),2.01-2.16 (m, 1H), 1.86-1.98 (m, 1H), 1.68-1.84 (m, 2H), 1.58- 1.66 (m,1H) 531 600 MHz 7.46 (t, J = 9.14 Hz, 1H), 7.41 (t, J = 8.98 Hz, 1H), —— DMSO - 5.00-5.12 (m, 2H), 4.35-4.46 (m, 1H), 3.82 (br s, d₆ 1H),3.49-3.82 (m, 7H), 3.23-3.30 (m, 1H), 2.94- 3.11 (m, 2H), 2.79 (dd, J =8.06, 12.57 Hz, 1H), 2.06- 2.17 (m, 1H), 2.00 (br s, 1H), 1.73-1.92 (m,2H), 0.71-0.80 (m, 4H) 532 600 MHz 7.46 (dd, J = 7.47, 11.13 Hz, 1H),7.37 (dd, J = 7.40, — — DMSO - 10.74 Hz, 1H), 7.30 (br d, J = 5.37 Hz,1H), 6.82 (br d₆ s, 1H), 4.95-5.06 (m, 2H), 4.31-4.45 (m, 1H), 4.22-4.30 (m, 1H), 3.97 (br d, J = 13.16 Hz, 1H), 3.10- 3.22 (m, 2H),2.91-3.09 (m, 3H), 2.66-2.82 (m, 2H), 2.35-2.47 (m, 1H), 2.00-2.16 (m,1H), 1.77-1.85 (m, 2H), 1.71-1.77 (m, 1H), 1.56-1.68 (m, 1H), 1.36- 1.44(m, 1H) 533 600 MHz 7.36 (t, J = 9.19 Hz, 1H), 6.93 (s, 1H), 6.89 (s,1H), — — DMSO - 6.80 (dt, J = 7.32, 10.20 Hz, 1H), 4.27-4.45 (m, 1H), d₆3.63-3.75 (m, 2H), 3.59 (br d, J = 11.83 Hz, 1H), 3.11-3.25 (m, 1H),2.98-2.74-2.92 (m, 3H), 1.90- 2.05 (m, 1H), 1.58-1.72 (m, 2H), 1.44 (d,J = 7.08 Hz, 3H), 1.36 (d, J = 7.24 Hz, 3H) 534 600 MHz 7.77 (br dd, J =4.44, 7.32 Hz, 1H), 7.46 (dd, J = 7.43, — — DMSO - 11.09 Hz, 1H), 7.37(dd, J = 7.36, 10.70 Hz, 1H), d₆ 4.94-5.07 (m, 2H), 4.32-4.44 (m, 1H),4.24-4.31 (m, 1H), 3.98 (br d, J = 13.23 Hz, 1H), 3.26 (br s, 1H),3.09-3.21 (m, 1H), 2.92-3.07 (m, 2H), 2.66-2.81 (m, 2H), 2.58 (d, J =4.59 Hz, 3H), 2.32-2.47 (m, 2H), 2.10 (br dd, J = 3.54, 13.20 Hz, 1H),1.57-1.86 (m, 4H), 1.33-1.46 (m, 1H) 535 600 MHz 7.32-7.49 (m, 2H),4.89-5.05 (m, 2H), — — DMSO - 4.34-4.45 (m, 1H), 3.69-3.85 (m, 2H),3.16-3.27 (m, d₆ 1H), 2.95-3.12 (m, 4H), 2.72-2.88 (m, 1H), 1.98- 2.16(m, 2H), 1.86 (br d, J = 1.71 Hz, 4H), 1.70-1.84 (m, 3H), 1.40-1.59 (m,2H) 536 600 MHz 7.46 (dd, J = 7.47, 11.13 Hz, 1H), 7.38 (dd, J = 7.36, —— DMSO - 10.70 Hz, 1H), 4.95-5.08 (m, 2H), 4.35-4.44 (m, d₆ 3H), 3.98(br d, J = 13.31 Hz, 1H), 3.49 (br s, 2H), 3.38-3.45 (m, 3H), 3.16-3.28(m, 2H), 2.91-3.04 (m, 3H), 2.71-2.83 (m, 2H), 1.97-2.15 (m, 1H), 1.73-1.91 (m, 1H), 1.57-1.70 (m, 4H), 1.51 (br s, 2H), 1.36-1.46 (m, 3H) 537600 MHz 7.46 (dd, J = 7.43, 11.09 Hz, 1H), 7.38 (dd, J = 7.40, — —DMSO - 10.74 Hz, 1H), 4.95-5.08 (m, 2H), 4.28-4.39 (m, d₆ 1H), 3.99 (brd, J = 13.39 Hz, 1H), 3.52 (br t, J = 5.99 Hz, 2H), 3.37-3.44 (m, 2H),3.25-3.30 (m, 1H), 3.13-3.25 (m, 2H), 2.94-3.05 (m, 2H), 2.85-2.93 (m,1H), 2.70-2.85 (m, 2H), 2.11 (ddd, J = 4.44, 8.19, 12.51 Hz, 1H),1.74-1.84 (m, 2H), 1.63-1.72 (m, 5H), 1.58 (quin, J = 5.90 Hz, 2H),1.40-1.53 (m, 5H) 538 600 MHz 7.47 (dd, J = 7.43, 11.17 Hz, 1H), 7.31(dd, J = 7.28, — — DMSO - 10.70 Hz, 1H), 5.03 (br s, 2H), 4.31-4.46 (m,2H), d₆ 3.55-3.71 (m, 4H), 3.34-3.42 (m, 4H), 3.21-3.28 (m, 3H),3.04-3.20 (m, 2H), 2.92-3.03 (m, 2H), 2.69- 2.81 (m, 1H), 2.26-2.40 (m,2H), 1.99-2.14 (m, 1H), 1.70-1.86 (m, 1H) 539 600 MHz 7.46 (dd, J =7.47, 11.13 Hz, 1H), 7.38 (dd, J = 7.40, — — DMSO - 10.74 Hz, 1H), 5.01(dq, J = 9.61, 17.43 Hz, 2H), d₆ 4.43 (td, J = 4.02, 7.61 Hz, 1H),4.31-4.38 (m, 1H), 4.29 (br s, 1H), 3.98 (br d, J = 13.23 Hz, 1H), 3.83-3.92 (m, 1H), 3.15-3.29 (m, 2H), 2.92-3.04 (m, 4H), 2.73-2.81 (m, 2H),2.51-2.62 (m, 1H), 2.06-2.15 (m, 1H), 1.71-1.88 (m, 4H), 1.59-1.71 (m,4.H), 1.39 (br s, 2H), 1.09-1.17 (m, 1H), 0.90 (br d, J = 6.38 Hz, 2H),0.85 (br d, J = 6.46 Hz, 2H) 540 600 MHz 7.46 (t, J = 9.12 Hz, 1H), 7.40(t, J = 9.00 Hz, 1H), — — DMSO - 5.00-5.11 (m, 2H), 4.33-4.44 (m, 1H),3.51-3.63 d₆ (m, 5H), 3.43-3.49 (m, 3H), 3.23-3.30 (m, 1H), 2.94-3.06(m, 2H), 2.79 (dd, J = 8.06, 12.57 Hz, 1H), 2.02-2.17 (m, 4H), 1.75-1.93(m, 2H) 541 600 MHz 7.47 (t, J = 9.15 Hz, 1H), 7.30-7.41 (m, 1H), 4.99-— — DMSO - 5.17 (m, 2H), 4.30-4.44 (m, 1H), 4.06-4.15 (m, 1H), d₆3.85-3.93 (m, 1H), 3.71-3.79 (m, 1H), 3.45-3.64 (m, 2H), 3.35-3.42(m,1H), 3.17 (d, J = 4.98 Hz, 1H), 3.05-3.13 (m, 1H), 2.93-3.04 (m, 2H),2.69-2.80 (m, 1H), 2.30-2.47 (m, 2H), 2.02-2.13 (m, 2H), 1.91- 1.96 (m,1H), 1.74-1.90 (m, 4H), 1.46-1.54 (m, 1H) 542 600 MHz 7.46 (dd, J =7.47, 11.13 Hz, 1H), 7.38 (dd, J = 7.32, — — DMSO - 10.74 Hz, 1H),4.95-5.07 (m, 2H), 4.67 (spt, J = 6.76 d₆ Hz, 1H), 4.29-4.37 (m, 1H),4.25 (td, J = 3.24, 6.52 Hz, 1H), 3.99 (br d, J = 13.47 Hz, 1H),3.17-3.35 (m, 1H), 2.92-3.05 (m, 3H), 2.86 (s, 2H), 2.69-2.83 (m, 2H),2.66 (s, 1H), 2.06-2.16 (m, 1H), 1.74-1.91 (m, 3H), 1.59-1.70 (m, 3H),1.35-1.47 (m, 1H), 1.16 (dd, J = 2.57, 6.31 Hz, 3H), 1.02 (dd, J = 3.58,6.62 Hz, 3H) 543 600 MHz 7.47-7.55 (m, 1H), 7.26-7.33 (m, 1H), 5.06-5.14(m, — — DMSO - 2H), 4.38-4.56 (m, 2H), 4.11-4.27 (m, 1H), 3.36- d₆ 3.46(m, 1H), 3.11-3.28 (m, 3H), 2.93-3.09 (m, 2H), 2.79 (br s, 1H),1.99-2.16 (m, 2H), 1.74 (br t, J = 9.42 Hz, 1H), 0.98 (d, J = 6.54 Hz,3H), 0.83 (dd, J = 2.34, 6.62 Hz, 3H) 544 600 MHz 6.80-6.88 (m, 1H),6.56-6.63 (m, 1H), 5.03-5.14 (m, B SFC: DMSO - 2H), 4.38-4.53 (m, 1H),4.30-4.37 (m, 1H), 4.23 (q, Chiralpak d₆ J = 9.52 Hz, 2H), 3.73-3.77 (m,3H), 3.24 (s, 3H), IC, 20% 2.92-3.04 (m, 3H), 2.72-2.82 (m, 1H),2.03-2.13 (m, methanol. Peak 1 1H), 1.73-1.90 (m, 1H) 545 600 MHz 6.83(dd, J = 2.18, 9.42 Hz, 1H), 6.61 (dd, J = 2.18, B SFC: DMSO - 11.99 Hz,1H), 4.96-5.07 (m, 2H), 4.34-4.44(m, Chiralpak d₆ 1H), 3.80 (s, 3H),3.63-3.70 (m, 2H), 3.59 (br d, IC, 35% J = 4.83 Hz, 4H), 3.40-3.52 (m,3H), 3.22-3.28 (m, methanol Peak 1 1H), 2.94-3.11 (m, 2H), 2.77 (dd, J =8.49, 12.53 Hz, 1H), 2.02-2.19 (m, 1H), 1.75-1.84 (m, 1H) 546 600 MHz6.74 (dd, J = 2.26, 8.95 Hz, 1H), 6.57 (dd, J = 2.22, B SFC: DMSO -12.18 Hz, 1H), 4.94-5.02 (m, 2H), 4.35-4.43 (m, Chiralpak d₆ 1H), 3.89(s, 3H), 3.61-3.70 (m, 2H), 3.59 (br s, IC, 35% 3H), 3.36-3.53 (m, 3H),3.16-3.28 (m, 2H), 2.92- methanol Peak 2 3.02 (m, 2H), 2.74 (dd, J =8.17, 12.46 Hz, 1H), 1.98- 2.14 (m, 1H), 1.74-1.86 (m, 1H) 547 500 MHz,7.35 (dd, J = 7.53, 10.64 Hz, 1H), 7.01 (dd, J = 6.88, B SC: METHANOL-10.25 Hz, 1H), 5.38 (t, J = 10.12 Hz, 1H), 4.34-4.52 Regis d4 (m, 1H),3.59-3.69 (m, 1H), 3.55 (dt, J = 7.40, 9.67 Whelk-O, Hz, 1H), 3.41-3.51(m, 2H), 3.05-3.22 (m, 2H), 2.94 30% IPA, (dd, J = 8.82, 12.46 Hz, 1H),2.79-2.87 (m, 1H), Peak 1 2.61-2.70 (m, 1H), 2.37-2.48 (m, 1H),2.18-2.30 (m, 1H), 1.91-2.03 (m, 1H), 0.80-0.94 (m, 4H) 548 500 MHz,7.39 (dd, J = 7.27, 10.64 Hz, 1H), 6.69 (dd, J = 7.01, B SC: CHLOROFORM-9.86 Hz, 1H), 5.21 (t, J = 9.99 Hz, 1H), 4.27-4.46 (m, Chiralpak d 2H),4.04-4.16 (m, 2H), 3.48-3.70 (m, 6H), 3.14- IC, 20% 3.24 (m, 1H),2.96-3.11 (m, 2H), 2.53-2.63 (m, 1H), methanol, Peak 1 2.41 (qd, J =9.54, 13.43 Hz, 1H), 2.18-2.26 (m, 1H), 1.92-2.08 (m, 2H), 1.69-1.91 (m,3H) 549 500 MHz, 7.36 (dd, J = 7.27, 10.64 Hz, 1H), 7.02 (dd, J = 7.01,B SC: METHANOL- 10.38 Hz, 1H), 5.39 (t, J = 10.12 Hz, 1H), 4.35-4.53Regis d4 (m, 1H), 3.64 (dt, J = 1.04, 9.73 Hz, 1H), 3.50-3.60 Whelk-O,(m, 2H), 3.41 (br dd, J = 5.19, 7.27 Hz, 1H), 3.11- 30% IPA, 3.21 (m,2H), 2.93 (dd, J = 8.56, 12.46 Hz, 1H), Peak 2 2.79-2.87 (m, 1H),2.57-2.67 (m, 1H), 2.42 (qd, J = 9.87, 12.94 Hz, 1H), 2.17-2.30 (m, 1H),1.94- 2.04 (m, 1H), 0.78-0.94 (m, 4H) 550 500 MHz, 7.39 (dd, J = 7.40,10.51 Hz, 1H), 6.69 (dd, J = 6.75, B SC: CHLOROFORM- 9.86 Hz, 1H), 5.19(t, J = 9.86 Hz, 1H), 4.35-4.47 (m, Chiralpak IC, d 2H), 4.02-4.19 (m,2H), 3.40-3.71 (m, 6H), 3.16- 2.0% 3.38 (m, 2H), 2.89 (dd, J = 8.69,12.59 Hz, methanol, 1H), 2.58 (dddd, J = 1.30, 7.72, 9.34, 13.30 Hz,1H), Peak 2 2.40 (qd, J = 9.68, 13.27 Hz, 1H), 2.16-2.32 (m, 1H),1.90-2.04 (m, 2H), 1.72-1.90 (m, 3H) 551 600 MHz, 7.46-7.56 (m, 2H),7.38-7.45 (m, 1H), 5.56 (s, 2H), — — DMSO- 4.32-4.50 (m, 1H), 3.37-3.51(m, 2H), 3.04-3.12 (m, d₆ 1H), 2.94-3.04 (m, 1H), 2.80-2.90 (m, 1H),2.07- 2.17 (m, 1H), 1.73-1.85 (m, 1H) 552 500 MHz, 7.06-7.14 (m, 1H),6.80-6.91 (m, 1H), 5.76 (s, 2H), B Regis Whelk- METHANOL- 4.54-4.72 (m,1H), 3.66-3.79 (m, 1H), 3.52-3.61 (m, O s, s, 25% d₄ 1H), 3.41-3.52 (m,1H), 3.32 (t, J = 1.62 Hz, 3H), MeOH, peak 2 3.15-3.24 (m, 1H),3.07-3.15 (m, 1H), 2.22-2.34 (m, 1H), 1.93-2.09 (m, 1H) 553 600 MHz,7.46-7.63 (m, 2H), 5.68-5.79 (m, 2H), 4.32-4.52 (m, — — DMSO- 1H),3.37-3.47 (m, 2H), 2.98-3.11 (m, 2H), 2.79- d₆ 2.88 (m, 1H), 2.62-2.69(m, 3H), 2.07-2.17 (m, 1H), 1.75-1.85 (m, 1H) 554 500 MHz, 7.54-7.67 (m,2H), 7.43-7.53 (m, 1H), 5.21 (s, 2H), F Chiralpak METHANOL- 4.10-4.57(m, 3H), 3.52-3.62 (m, 1H), 3.39-3.47 (m, AD-H, 15% MeOH/ d₄ 1H), 3.35(s, 3H), 3.13 (m, 2H), 2.92-3.06 (m, 1H), DEA, peak 1 2.12-2.28 (m, 1H),1.86-2.03 (m, 1H) 555 500 MHz, 8.81 (s, 2H), 8.16 (t, J = 2.34 Hz, 1H),7.58 (dd, F Chiralpak METHANOL- J = 2.59, 8.43 Hz, 1H), 5.54 (s, 2H),4.36-4.56 (m, IC, 40% MeOH d₄ 1H), 3.68-3.79 (m, 1H), 3.58-3.68 (m, 1H),3.10- with 0.2% 3.25 (m, 2H), 2.96-3.10 (m, 1H), 2.10-2.27 (m, 1H), DEA,peak 2 1.81-1.97 (m, 1H) 556 600 MHz, 8.98 (d, J = 1.79 Hz, 1H),8.29-8.34 (m, 1H), 7.53 (d, B Lux Cellulose- DMSO- J = 8.25 Hz, 1H),7.01-7.06 (m, 1H), 6.97 (td, 2, 30% d₆ J = 10.59, 2.18 Hz, 1H), 5.57 (s,2H), 4.32-4.40 (m, MeOH, peak 2 1H), 3.36-3.51 (m, 2H), 3.31 (s, 3H),2.98-3.09 (m, 1H), 2.86-2.95 (m, 1H), 2.80 (dd, J = 12.46, 8.49 Hz, 1H),2.01-2.09 (m, 1H), 1.68-1.76 (m, 1H) 557 500 MHz, 7.2.1-7.40 (m, 1H),7.07-7.17 (m, 1H), 6.81-6.93 (m, B Regis Whelk- METHANOL- 1H), 5.83-5.96(m, 2H), 4.63-4.80 (m, 1H), 3.73- O s, s, 10% d₄ 3.86 (m, 1H), 3.54-3.72(m, 2H), 3.12-3.25 (m, 2H), MeOH, peak 2 2.24-2.36 (m, 1H), 1.98-2.10(m, 1H) 558 500 MHz, 7.00-7.08 (m, 1H), 6.74-6.84 (m, 1H), 5.19 (s, 2H),F Regis Whelk- METHANOL- 4.38-4.56 (m, 1H), 4.06-4.28 (m, 3H), 3.48-3.58(m, O s, s, 15% d₄ 1H), 3.38-3.46 (m, 1H), 3.33 (s, 3H), 3.14-3.20 (m,MeOH, peak 1 1H), 2.88-3.02 (m, 1H), 2.14-2.27 (m, 1H), 1.88- 2.00 (m,1H) 559 500 MHz, 7.39-7.50 (m, 1H), 7.22-7.34 (m, 1H), 7.09-7.23 (m, FChiralpak METHANOL- 1H), 5.10 (s, 2H), 4.11-4.53 (m, 3H), 3.44-3.55 (m,AD-H, 25% MeOH/ d₄ 1H), 3.34-3.41 (m, 1H), 3.34 (s, 3H), 3.05-3.16 (m,DEA, peak 1 2H), 2.87-2.98 (m, 1H), 2.12-2.25 (m, 1H), 1.82- 2.00 (m,1H) 560 600 MHz 7.42-7.68 (m, 3H), 5.84-5.98 (m, 2H), 4.30-4.51 (m, — —DMSO- 1H), 3.34-3.49 (m, 2H), 3.04-3.13 (m, 1H), 2.93- d₆ 3.02 (m, 1H),2.79-2.90 (m, 1H), 2.08-2.18 (m, 1H), 1.73-1.86 (m, 1H) 561 500 MHz,7.43-7.54 (m, 1H), 7.16-7.27 (m, 1H), 6.94-7.04 (m, B ChiralpakMETHANOL- 1H), 5.75 (s, 2H), 4.54-4.74 (m, 1H), 3.66-3.75 (m, AZ-H, 30%d₄ 1H), 3.51-3.59 (m, 1H), 3.43-3.49 (m, 1H), 3.28- MeOH, peak 2 3.36(m, 3H), 3.06-3.24 (m, 2H), 2.22-2.39 (m, 1H), 1.96-2.14 (m, 1H) 562 600MHz, 8.92-9.00 (m, 1H), 8.26-8.35 (m, 1H), 7.44-7.57 (m, — — DMSO- 2H),7.32-7.42, (m, 1H), 5.55 (s, 2H), 4.29-4.48 (m, d₆ 1H), 3.38-3.47 (m,2H), 3.31 (s, 3H), 2.99-3.09 (m, 1H), 2.89-2.98 (m, 1H), 2.75-2.84 (m,1H), 2.00- 2.11 (m, 1H), 1.65-1.78 (m, 1H) 563 600 MHz, 7.64 (s, 1H),7.56 (d, J = 8.33 Hz, 1H), 7.40 (dd, B Chiralpak DMSO- J = 8.33, 1.25Hz, 1H), 5.06-5.15 (m, 2H), 4.38-4.46 IC, 15% MeOH, d₆ (m, 1H),3.39-3.41 (m, 2H), 3.07-3.15 (m, 4H), 2.99 peak 1 (m, 1H), 2.90 (s, 3H),2.84 (dd, J = 12.69, 8.17 Hz, 1H), 2.01-2.17 (m, 1H), 1.74-1.85 (m, 1H)564 600 MHz, 7.47-7.52 (m, 1H), 7.42-7.46 (m, 1H), 6.07-6.14 (m, — —DMSO- 1H), 5.34 (s, 2H), 4.31-4.55 (m, 1H), 3.40-3.51 (m, d₆ 2H),2.98-3.12 (m, 2H), 2.79-2.89 (m, 1H), 2.36 (s, 3H), 2.07-2.18 (m, 1H),1.75-1.85 (m, 1H) 565 600 MHz, 7.02-7.09 (m, 1H), 6.90-6.98 (m, 1H),4.94-5.05 (m, B Phenomenex DMSO- 2H), 4.31-4.49 (m, 1H), 3.32 (s, 2H),3.12 (s, 3H), CEL 2, 25% d₆ 2.93-3.07 (m, 2H), 2.88 (s, 3H), 2.75-2.82(m, 1H), MeOH, peak 1 2.04-2.18 (m, 1H), 1.77-1.83 (m, 1H) 566 600 MHz,7.35-7.44 (m, 1H), 7.07-7.13 (m, 1H), 6.84-6.95 (m, B Phenomenex DMSO-1H), 4.90-5.04 (m, 2H), 4.31-4.49 (m, 1H), 3.24- CEL 2, 25% d₆ 3.25 (m,2H), 3.12 (s, 3H), 2.93-3.03 (m, 2H), 2.89 MeOH, peak 1 (s, 3H),2.72-2.81 (m, 1H), 2.03-2.17 (m, 1H), 1.73- 1.86 (m, 1H) 567 600 MHz,7.49-7.54 (m, 1H), 7.40-7.46 (m, 1H), 6.77-6.87 (m, — — DMSO- 1H), 5.40(s, 2H), 4.30-4.48 (m, 1H), 3.37-3.50 (m, d₆ 2H), 3.03-3.13 (m, 1H),2.91-3.00 (m, 1H), 2.80- 2.88 (m, 1H), 2.26 (d, J = 1.09 Hz, 3H),2.06-2.15 (m, 1H), 1.72-1.81 (m, 1H) 568 600 MHz, 7.47-7.57 (m, 2H),7.18-7.28 (m, 1H), 5.59 (s, 2H), — — DMSO- 4.31-4.48 (m, 1H), 3.38-3.51(m, 2H), 3.03-3.12 (m, d₆ 1H), 2.92-3.01 (m, 1H), 2.79-2.88 (m, 1H),2.32 (s, 3H), 2.04-2.17 (m, 1H), 1.73-1.81 (m, 1H) 569 600 MHz,7.45-7.53 (m, 1H), 7.35-7.42 (m, 1H), 6.96-7.06 (m, B Chiralcel DMSO-1H), 5.89 (s, 2H), 4.28-4.47 (m, 1H), 3.32 (m, 2H), OD-H, 15% d₆2.97-3.06 (m, 1H), 2.87-2.95 (m, 1H), 2.73-2.82 (m, isopropanol, 1H),2.04-2.14 (m, 1H), 1.67-1.77 (m, 1H) peak 1 570 500 MHz, 7.42-7.52 (m,1H), 7.09-7.21 (m, 2H), 5.11 (s, 2H), F Chiralpak METHANOL- 4.09-4.53(m, 3H), 3.46-3.56 (m, 1H), 3.35-3.45 (m, AD-H 25% MeOH/ d₄ 1H), 3.34(s, 3H), 3.05-3.15 (m, 2H), 2.87-2.98 (m, DEA, peak 2 1H), 2.13-2.26 (m,1H), 1.85-1.97 (m, 1H) 571 600 MHz, 7.48-7.57 (m, 2H), 5.59 (s, 2H),4.32-4.50 (m, 1H), — — DMSO- 3.39-3.46 (m, 2H), 3.02-3.10 (m, 1H),2.94-3.02 (m, d₆ 1H), 2.76-2.88 (m, 1H), 2.47 (s, 3H), 2.06-2.17 (m,1H), 1.73-1.82 (m, 1H) 572 600 MHz, 7.48-7.56 (m, 1H), 7.39-7.47 (m,1H), 5.44 (s, 2H), — — DMSO- 4.31-4.50 (m, 1H), 3.35-3.48 (m, 2H),3.02-3.13 (m, d₆ 1H), 2.91-3.01 (m, 1H), 2.78-2.89 (m, 1H), 2.57 (s,3H), 2.06-2.16 (m, 1H), 1.72-1.80 (m, 1H) 573 500 MHz, 7.47-7.56 (m,1H), 7.10-7.37 (m, 2H), 6.99-7.07 (m, B Chiralcel METHANOL- 1H), 5.90(s, 2H), 4.65-4.84 (m, 1H), 3.75-3.84 (m, OD-H, 15% d₄ 1H), 3.53-3.70(m, 2H), 3.13-3.23 (m, 2H), 2.26- isopropanol, 2.37 (m, 1H), 2.00-2.11(m, 1H) peak 1 574 500 MHz, 8.18-8.24 (m, 1H), 7.68-7.75 (m, 1H),5.73-5.82 (m, B Chiralpak METHANOL- 2H), 4.54-4.74 (m, 1H), 3.77-3.88(m, 1H), 3.41- IC, 35% d₄ 3.77 (m, 2H), 3.32 (td, J = 1.62, 3.24 Hz,1H), 3.06- MeOH, peak 1 3.22 (m, 1H), 2.68-2.79 (m, 3H), 2.21 (s, 1H),1.90- 2.05 (m, 1H) 575 600 MHz, 7.47-7.55 (m, 1H), 7.36-7.46 (m, 1H),5.35 (s, 2H), — — DMSO- 4.32-4.48 (m, 1H), 3.39-3.49 (m, 2H), 3.03-3.12(m, d₆ 1H), 2.93-3.02 (m, 1H), 2.79-2.89 (m, 1H), 2.18 (s, 3H),2.05-2.14 (m, 1H), 1.97 (s, 3H), 1.70-1.82 (m, 1H) 576 600 MHz,7.20-7.24 (m, 1H), 7.12-7.19 (m, 1H), 6.86-6.95 (m, B Chiralpak DMSO-1H), 4.91-5.05 (m, 2H), 4.31-4.48 (m, 1H), 3.33- IC, 15% d₆ 3.39 (m,2H), 3.12 (s, 3H), 2.93-3.06 (m, 2H), 2.89 MeOH, peak 2 (s, 3H),2.74-2.82 (m, 1H), 2.05-2.15 (m, 1H), 1.74- 1.82, (m, 1H) 577 600 MHz,7.42-7.54 (m, 2H), 5.45 (s, 2H), 4.29-4.49 (m, 1H), — — DMSO- 3.37-3.50(m, 2H), 3.03-3.13 (m, 1H), 2.92 (m, 3H), d₆ 2.77-2.87 (m, 1H),2.06-2.17 (m, 1H), 1.71-1.80 (m, 1H), 1.24 (t, J = 7.55 Hz, 3H) 578 600MHz, 7.43-7.56 (m, 2H), 5.37-5.45 (m, 2H), 4.31-4.49 (m, — — DMSO- 1H),3.36-3.47 (m, 2H), 3.03-3.11 (m, 1H), 2.90- d₆ 2.99 (m, 1H), 2.75-2.86(m, 1H), 2.29-2.37 (m, 1H), 2.05-2.17 (m, 1H), 1.69-1.82 (m, 1H),1.20-1.27 (m, 3H), 1.03-1.10 (m, 3H) 579 600 MHz, 7.45-7.58 (m, 2H),6.28-6.36 (m, 1H), 5.45 (s, 2H), — — DMSO- 4.32-4.51 (m, 1H), 3.39-3.47(m, 1H), 3.35-3.39 (m, d₆ 1H), 3.04-3.13 (m, 1H), 2.94-3.03 (m, 1H),2.79- 2.89 (m, 1H), 2.19 (s, 3H), 2.08-2.16 (m, 1H), 1.78- 1.84 (m, 1H)580 500 MHz, 7.70-7.83 (m, 1H), 7.42-7.53 (m, 1H), 7.27-7.41 (m, FChiralpak METHANOL- 1H), 5.21 (s, 2H), 4.13-4.56 (m, 3H), 3.51-3.62 (m,AD-H, 15% MeOH/ d₄ 1H), 3.40-3.48 (m, 1H), 3.37 (s, 3H), 3.12 (s, 2H),DEA, peak 2 2.93-3.05 (m, 1H), 2.14-2.30 (m, 1H), 1.88-2.03 (m, 1H) 581600 MHz, 7.47-7.61 (m, 2H), 5.48-5.60 (m, 2H), 4.30-4.49 (m, — — DMSO-1H), 3.37-3.46 (m, 2H), 2.99-3.08 (m, 1H), 2.90- d₆ 2.98 (m, 1H),2.78-2.86 (m, 1H), 2.18-2.25 (m, 1H), 2.06-2.16 (m, 1H), 1.72-1.81 (m,1H), 1.08-1.15 (m, 2H), 0.91-0.99 (m, 2H) 582 500 MHz, 7.33-7.40 (m,1H), 7.16-7.25 (m, 1H), 6.92-7.01 (m, B Chiralpak METHANOL- 1H),5.70-5.80 (m, 2H), 4.48-4.68 (m, 1H), 3.65- AZ-H, 30% d₄ 3.75 (m, 1H),3.50-3.59 (m, 1H), 3.36 (s, 3H), 3.30- MeOH, peak 1 3.34 (m, 1H),3.14-3.25 (m, 1H), 3.02-3.12 (m, 1H), 2.22-2.34 (m, 1H), 1.93-2.07 (m,1H) 583 500 MHz, 8.70-8.80 (m, 2H), 7.94-8.04 (m, 1H), 7.56-7.66 (m, FChiralpak METHANOL- 1H), 5.62 (s, 2H), 4.39-4.61 (m, 1H), 3.63-3.87 (m,IC, 40% MeOH d₄ 2H), 3.13-3.25 (m, 2H), 2.95-3.09 (m, 1H), 2.12- with0.2% 2.26 (m, 1H), 1.74-1.92 (m, 1H) DEA, peak 2 584 600 MHz, 7.37-7.45(m, 1H), 7.26-7.35 (m, 1H), 6.95-7.06 (m, B Chiralcel DMSO- 1H), 5.89(s, 2H), 4.30-4.49 (m, 1H), 3.32-3.44 (m, OD-H, 15% d₆ 2H), 3.00-3.11(m, 1H), 2.86-2.97 (m, 1H), 2.75- isopropanol, 2.84 (m, 1H), 2.06-2.17(m, 1H), 1.67-1.77 (m, 1H) peak 2 585 600 MHz, 7.77-7.84 (m, 2H),7.39-7.47 (m, 4H), 7.30 (dd, B Chiralcel DMSO- J = 9.23, 2.45 Hz, 1H),6.95 (ddd, J = 10.02, 8.66, OJ-H, 30% d₆ 2.57 Hz, 1H), 5.48-5.55 (m,2H), 4.34-4.48 (m, 1H), MeOH, peak 1 3.37-3.51 (m, 2H), 3.03-3.12 (m,2H), 2.84 (dd, J = 12.42, 8.91 Hz, 1H), 2.52 (s, 3H), 2.12-2.21 (m, 1H),1.79-1.97 (m, 1H) 586 600 MHz, 7.46-7.55 (m, 1H), 7.26-7.35 (m, 1H),5.45 (s, 2H), — — DMSO- 4.30-4.49 (m, 1H), 3.39 (s, 5H), 2.96-3.11 (m,2H), d₆ 2.78-2.88 (m, 1H), 2.26-2.32 (m, 3H), 2.06-2.18 (m, 1H),1.77-1.86 (m, 1H) 587 500 MHz, 7.35-7.42 (m, 1H), 7.23 (s, 2H),6.95-7.03 (m, 1H), B Chiralcel METHANOL- 5.90 (s, 2H), 4.50-4.70 (m,1H), 3.67-3.77 (m, 1H), OD-H, 15% d₄ 3.54-3.63 (m, 1H), 3.37-3.49 (m,1H), 3.15-3.25 (m, isopropanol, 1H), 3.02-3.13 (m, 1H), 2.21-2.33 (m,1H), 1.94- peak 2 2.08 (m, 1H) 588 500 MHz, 7.43-7.52 (m, 1H), 7.17-7.25(m, 1H), 6.95-7.04 (m, B Chiralcel METHANOL- 1H), 5.77 (d, J = 1.95 Hz,2H), 3.50-3.61 (m, 1H), OD-H, 10% d₄ 3.40-3.49 (m, 1H), 3.29-3.35 (m,2H), 3.14-3.25 (m, isopropanol, 1H), 2.73 (s, 3H), 2.29-2.45 (m, 1H),2.14-2.30 (m, peak 1 1H) 589 600 MHz, 7.37-7.44 (m, 1H), 7.19-7.27 (m,1H), 6.89-6.97 (m, B Chiralcel DMSO- 1H), 5.34-5.44 (m, 2H), 4.30-4.49(m, 1H), 3.37- OJ-H, 10% d₆ 3.47 (m, 2H), 2.97-3.11 (m, 2H), 2.75-2.85(m, 1H), isopropanol, 2.46-2.48 (m, 3H), 2.39 (s, 3H), 2.09-2.19 (m,1H), peak 1 1.81-1.91 (m, 1H) 590 500 MHz, 7.86-7.98 (m, 1H), 7.34-7.49(m, 1H), 6.05 (s, 2H), B Chiralpak METHANOL-d₄ 4.65-4.85 (m, 2H),4.48-4.63 (m, 1H), 3.13-3.48 (m, IC, 35% 3H), 2.75 (s, 3H), 2.25-2.38(m, 1H), 1.77-1.94 (m, MeOH, peak 2 1H) 591 500 MHz, 6.87-6.95 (m, 1H),6.74-6.86 (m, 1H), 5.07-5.21 (m, F Regis Whelk- METHANOL-d₄ 2H),4.12-4.56 (m, 3H), 3.45-3.59 (m, 1H), 3.36 (s, O s, s, 15% 3H),2.89-3.23 (m, 4H), 2.11-2.28 (m, 1H), 1.84- MeOH, peak 2 1.99 (m, 1H)592 600 MHz, 7.73 (s, 1H), 7.39 (s, 2H), 5.03-5.12 (m, 2H), B ChiralpakDMSO- 4.37-4.46 (m, 1H), 3.36-3.44 (m, 2H), 3.14 (s, IC, 15% d₆ 3H),2.96-3.12 (m, 2H), 2.89 (s, 3H), 2.84 (dd, MeOH, peak 2 J = 12.57, 8.29Hz, 1H), 2.08-2.17 (m, 1H), 1.81- 1.92 (m, 1H) 593 600 MHz, 7.76-7.83(m, 2H), 7.39-7.46 (m, 3H), 7.36 (dd, B Chiralcel DMSO- J = 8.76, 4.71Hz, 1H), 7.25 (dd, J = 9.73, 2.49 Hz, OJ-H, 30% d₆ 1H), 6.95 (ddd, J =9.85, 8.80, 2.53 Hz, 1H), 5.52 MeOH, peak 2 (s, 2H), 4.35-4.49 (m, 1H),3.39-3.54 (m, 2H), 3.03- 3.15 (m, 2H), 2.87 (dd, J = 12.42, 8.91 Hz,1H), 2.47 (s, 3H), 2.12-2.22 (m, 1H), 1.78-1.94 (m, 1H) 594 600 MHz,7.09-7.17 (m, 1H), 6.86-6.96 (m, 1H), 4.96-5.09 (m, B Phenomenex DMSO-2H), 4.32-4.50 (m, 1H), 3.22-3.43 (m, 2H), 3.10 (s, CEL 2, 25% d₆ 3H),2.96-3.07 (m, 2H), 2.89 (s, 3H), 2.77-2.85 (m, MeOH, peak 2 1H),2.07-2.18 (m, 1H), 1.74-1.87 (m, 1H) 595 600 MHz, 8.97 (d, J = 1.79 Hz,1H), 8.32 (dd, J = 8.25, 2.34 Hz, B Lux Cellulose- DMSO- 1H), 7.55 (d, J= 8.33 Hz, 1H), 7.17 (dd, J = 9.26, 2.18 2, 30% d₆ Hz, 1H), 6.88 (J =10.33 Hz, 1H), 5.54-5.61 (m, MeOH, peak 1 2H), 4.31-4.45 (m, 1H),3.39-3.45 (m, 2H), 3.04- 3.14 (m, 1H), 2.92-3.03 (m, 1H), 2.85 (dd, J =12.61, 8.49 Hz, 1H), 2.03-2.20 (m, 1H), 1.73-1.82 (m, 1H) 596 600 MHz,7.28-7.34 (m, 1H), 7.20-7.26 (m, 1H), 6.90-6.98 (m, B Chiralcel DMSO-1H), 5.40 (s, 2H), 4.33-4.49 (m, 1H), 3.40-3.53 (m, OJ-H, 10% d₆ 2H),3.01-3.14 (m, 2H), 2.80-2.89 (m, 1H), 2.45- isopropanol, 2.48 (m, 3H),2.39 (s, 3H), 2.10-2.21 (m, 1H), 1.80- peak 2 1.89 (m, 1H) 597 500 MHz,7.33-7.40 (m, 1H), 7.16-7.26 (m, 1H), 6.93-7.04 (m, B ChiralcelMETHANOL- 1H), 5.77 (d, J = 1.56 Hz, 2H), 3.54-3.63 (m, 1H), OD-H, 10%d₄ 3.44-3.52 (m, 1H), 3.37-3.43 (m, 1H), 3.32 (s, 1H), isopropanol,3.18-3.27 (m, 1H), 2.68-2.77 (m, 3H), 2.31-2.44 (m, peak 2 1H),2.14-2.30 (m, 1H) 598 500 MHz, 7.24 (t, J = 55 Hz, 1H), 7.08-7.16 (m,1H), 6.83-6.92 B Regis Whelk- METHANOL- (m, 1H), 5.94 (s, 2H), 4.70-4.86(m, 1H), 3.85-3.93 O s, s, 10% d₄ (m, 1H), 3.73-3.83 (m, 1H), 3.64-3.72(m, 1H), 3.24 MeOH, peak 1 (dd, J = 10.45, 12.65 Hz, 2H), 2.25-2.38 (m,1H), 2.08 (br dd, J = 1.36, 2.92 Hz, 1H) 599 500 MHz, 7.04-7.11 (m, 1H),6.80-6.92 (m, 1H), 5.79 (s, 2H), B Regis Whelk- METHANOL- 4.58-4.79 (m,1H), 3.74-3.84 (m, 1H), 3.52-3.68 (m, O s, s, 25% d₄ 2H), 3.12-3.27 (m,2H), 2.74 (s, 3H), 2.24-2.36 (m, MeOH, peak 1 1H), 1.99-2.10 (m, 1H)

Intermediate 86:4-((2,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile

Step 1. 4-(((5-chloro-2-nitrophenyl)amino)methyl)benzonitrile

To a stirred solution of 4-chloro-2-fluoro-1-nitrobenzene (8.0 g, 45.6mmol, 1 equiv) in ethanol (104.0 mL) and water (80.0 mL) was added4-(aminomethyl)benzonitrile hydrochloride (8.45 g, 50.1 mmol, 1.1 equiv)followed by addition of potassium carbonate (11.34 g, 82.0 mmol, 1.8equiv). The reaction mixture was heated to 85° C. for 10 h then stirredfor 8 h at ambient temperature. After completion (monitored by TLC), thereaction mixture was diluted with water (100 mL) and solids werefiltered. The obtained solid was dried under high vacuum to provide4-(((5-chloro-2-nitrophenyl)amino)methyl)benzonitrile (9 g. 68.6% yield)as yellow solid. ¹H NMR (400 MHz, DMSO-d₆): δ 8.85 (t, J=6.3 Hz 1H).8.08-8.13 (m, 1H), 7.86-7.79 (m, 2H), 7.56 (d, J=8.0 Hz, 2H), 6.90 (t,J=2.4 Hz, 1H), 6.77-6.66 (m, 1H), 4.76 (d, J=6.3 Hz, 2H).

Step 2. 4-(((2-amino-5-chlorophenyl)amino)methyl)benzonitrile

To a stirred solution of4-(((5-chloro-2-nitrophenyl)amino)methyl)benzonitrile (9.0 g, 31.3 mmol,1.0 equiv) in mixture of tetrahydrofuran (90.0 mL), methanol (90.0 mL)and water (60.0 mL) was added iron powder (7.51 g, 135.0 mmol, 4.3equiv) followed by ammonium chloride (7.53 g. 141.0 mmol, 4.5 equiv).The resulting reaction mixture was heated to 60° C. for 2 h. Aftercompletion (monitored by TLC), the reaction mixture was filtered throughcelite pad and was washed with ethyl acetate (100 mL). The filtrate wasdiluted with water (100 mL) and layers were separated, aqueous layer waswashed with ethyl acetate (2×200 mL). The combined organic layers werewashed with water (2×200 mL), brine (2×200 mL), dried over sodiumsulphate, filtered and concentrate under reduced pressure to provide4-(((2-amino-5-chlorophenyl)amino)methyl)benzonitrile (7.5 g, 93% yield)as light yellow solid which was sufficiently pure to use in the nextstep. ¹H NMR (400 MHz, DMSO-d₆): δ 7.81 (dd, J=8.3, 2.3 Hz, 2H),7.65-7.45 (m, 2H), 6.53 (dd. J=8.2, 2.2 Hz, 1H). 6.40 (dt, J=8.1, 2.4Hz, 1H), 6.19 (d, J=2.4 Hz, 1H). 5.58 (t, J=7.2 Hz, 1H), 4.75 (s, 2H),4.54-4.28 (m, 2H).

Step 3.4-((6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile

To a stirred solution of4-(((2-amino-5-chlorophenyl)amino)methyl)benzonitrile (7.5 g, 29.1 mmol,1.0 equiv) in 1,4-dioxane (120.0 mL) was added DIPEA (7.62 mL, 43.7mmol. 1.5 equiv) and CDI (11.80 g. 72.8 mmol, 2.5 equiv) portion wise.The resulting reaction mixture was heated to 100° C. for 1 h. Aftercompletion (monitored by TLC), the reaction mixture was cooled toambient temperature and slowly quenched with ice cold water (100 mL).The reaction mixture was extracted with ethyl acetate (2×150 mL). Thecombined organic layers were washed with water (2×150 mL) and brinesolution (2×100 mL), dried over sodium sulphate, filtered andconcentrate under reduced pressure to provide4-((6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile(6 g, 72.7% yield) as light brown solid which was sufficiently pure touse in next step as such. ¹H NMR (400 MHz, DMSO-d₆): δ 11.21 (s, 1H).7.86-7.79 (m, 2H). 7.54-7.40 (m, 2H), 7.23 (d. J=1.7 Hz. 1H), 7.06-6.97(m, 2H). 5.12 (s, 2H). MS: (ESI neg. ion) m/z: 282 [M−1]

Step 4. 4-((2,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile

To a stirred solution of4-((6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile(6.0 g. 21.15 mmol. 1.0 equiv) in POCl3 (60.0 mL) was heated to 110° C.for 5 h. After completion (monitored by TLC), the reaction mixture wasconcentrated under high vacuum pressure. The obtained residue wasdiluted with DCM and slowly neutralized with 10% aqueous sodiumbicarbonate solution at 0° C. The layers were separated and aqueouslayer was extracted with DCM (2×150 mL). The combined organic layerswere washed with water (200 mL), brine (200 mL), dried over sodiumsulphate, filtered and concentrated under reduced pressure. The obtainedcrude was purified on silica gel 230-400 mesh using petroleum ether andethyl acetate as an eluent (15-20%) to afford4-((2,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile (2.5 g,39.1% yield) as an off white solid. ¹H NMR (400 MHz, DMSO-d): δ7.91-7.79 (m, 3H), 7.68 (d, J=8.7 Hz. 1H), 7.39-7.28 (m, 3H). 5.67 (s,2H). MS: (ESI pos. ion) m/z: 302.0 [M+1]

TABLE 7 Intermediates accessed using the sequence outlines in Scheme 11Int MS # Structure Compound Name ¹H NMR MH+ 86

4-((2,6-dichloro-1H- benzo[d]imidazol-1- yl)methyl)benzonitrile ¹H NMR(400 MHz, DMSO-d₆): δ 7.91- 7.79 (m, 3H), 7.68 (d, J = 8.7 Hz, 1H),7.39-7.28 (m, 3H), 5.67 (s, 2H) 302.0 87

4-((2-chloro-6- ethoxy-1H- benzo[d]imidazol-1- yl)methyl)benzonitrile ¹HNMR (400 MHz, DMSO-d₆): δ 7.84 (dq, J = 8.5, 1.9 Hz, 2H), 7.52 (dd, J =8.8, 1.2 Hz, 1H), 7.34 (d, J = 8.2 Hz, 2H), 7.22 (d, J = 2.3 Hz, 1H),6.88 (dt, J = 8.8, 1.8 Hz, 1H), 5,62 (s, 2H), 4.02 (q, J = 7.0 Hz, 2H),1.32 (t, J = 7.0 Hz, 3H) 312.0 88

4-((2-chloro-1H- imidazo[4,5- b]pyridin-1- yl)methyl)benzonitrile ¹H NMR(400 MHz, DMSO-d₆): δ 11.74 (s, 1H), 7.93 (d, J = 5.1 Hz, 1H), 7.82 (d,J = 7.9 Hz, 2H), 7.49 (d, J = 7.8 Hz, 2H), 7.38 (d, J = 7.5 Hz, 1H),6.99 (dd, J = 7.7, 5.1 Hz, 1H), 5.14 (s, 2H) 251.2 89

4-((2-chloro-6-fluoro- 1H-benzo[d]imidazol- 1- yl)methyl)benzonitrile ¹HNMR (400 MHz, DMSO-d₆): δ 7.87- 7.81 (m, 2H), 7.71-7.59 (m, 2H), 7.39-7.33 (m, 2H), 7.15 (ddd, J = 10.0, 8.9, 2.5 Hz, 1H), 5.64 (s, 2H) 286.090

4-((2-chloro-1H- imidazo[4,5- c]pyridin-1- yl)methyl)benzonitrile —269.2 91

4-[(2-chloro-3H- imidazo[4,5- c]pyridin-3- yl)methyl)benzonitrile —269.2 92

4-((2,4-dichloro-1H- benzo[d]imidazol-1- yl)methyl)benzonitrile ¹H NMR(400 MHz, DMSO-d₆): δ 7.87- 7.80 (m, 2H), 7.65-7.58 (m, 1H), 7.42- 7.27(m, 4H), 5.70 (d, J = 2.8 Hz, 2H) 302.1 93

4-((2-chloro-3H- imidazo[4,5- b]pyridin-3- yl)methyl)benzonitrile ¹H NMR(400 MHz, DMSO-d₆): δ 8.41 (dd, J = 4.7, 2.0 Hz, 1H), 8.13 (dt, J = 8.1,1.7 Hz, 1H), 7.83 (dd, J = 8.3, 2.3 Hz, 2H), 7.46-7.34 (m, 3H), 5.64 (d,J = 2.2 Hz, 2H) 269.0 94

4-((2,7-dichloro-1H- benzo[d]imidazol-1- yl)methyl)benzonitrile 1H NMR(400 MHz, DMSO-d6): δ 7.84 (d, J = 8.1 Hz, 2H), 7.69 (dd, J = 7.8, 1.1Hz, 1H), 7.36 (dd, J = 7.9, 1.2 Hz, 1H), 7.32 (d, J = 7.8 Hz, 1H), 7.25(d, J = 8.1 Hz, 2H), 5.89 (s, 2H) 302.1 95

4-((2-chloro-6- methoxy-1H- benzo[d]imidazol-1- yl)methyl)benzonitrile —298.2 96

4-((2-chloro-5- methoxy-3H- imidazo[4,5- b]pyridin-3-yl)methyl)benzonitrile — 299.2 97

4-((2-chloro-4- methoxy-1H- benzo[d]imidazol-1- yl)methyl)benzonitrile¹H NMR (400 MHz, DMSO-d₆): δ 7.87- 7.80 (m, 2H), 7.36-7.27 (m, 2H),7.26- 7.14 (m, 2H), 6.81 (dd, J = 7.7, 1.3 Hz, 1H), 5.62 (s, 2H), 3.93(s, 3H) 298.2 98

4-((2,5-dichloro-1H- benzo[d]imidazol-1- yl)methyl)benzonitrile — 302.2

Step 1. 4-((2,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile

To a suspension of4-((2,6-dichloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile (50 mg,0.165 mmol, 1 equiv) and tert-butyl((3R,4R)-4-fluoropiperidin-3-yl)carbamate (72.2 mg. 0.331 mmol, 2 equiv)in 1-butanol (662 μl, 0.25 M) in a microwave vial was added DIEA (43.4μl, 0.248 mmol, 1.5 equiv). The vial was heated to 130° C. for 12 hours.The reaction mixture was cooled to room temperature, concentrated, andloaded onto a 12 g RediSep ISCO cartridge, eluting with 20-80% ethylacetate in heptane, to provide tert-butyl((3R,4R)-1-(6-chloro-1-(4-cyanobenzyl)-H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(40 mg, 49.9% yield) as a white solid. MS (ESI pos. ion) m/z: 484.0(M+H).

Step 2.4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrile

To a solution of tert-butyl((3R,4R)-1-(6-chloro-1-(4-cyanobenzyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(40 mg, 0.083 mmol. 1 equiv) in 1,4-dioxane (1 mL) was added 4 N HCl indioxane (0.517 mL, 2.066 mmol. 25 equiv). The reaction was stirred atambient temperature for 6 hours at which time the reaction mixture wasconcentrated to provide4-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)benzonitrilehydrochloride as a white solid. NMR (400 MHz, DMSO-d₆) 8.78 (br s, 2H),7.87-7.80 (m, 2H). 7.55 (d, J=8.5 Hz. 1H), 7.49-7.35 (m, 3H), 7.31-7.21(m, 1H), 5.65-5.49 (m, 2H), 5.05-4.91 (m, 1H), 3.95 (br d. J=12.3 Hz,1H), 3.79-3.61 (m, 1H), 3.52-3.44 (m, 1H), 3.35-3.22 (m, 1H). 3.12 (brt, J=11.5 Hz, 1H). 2.32-2.15 (m, 1H), 1.99-1.79 (m, 1H). MS (ESI pos.ion) m/z: 384.0 (M+H).

TABLE 8 Examples prepared in a manner analogous to Schemes 11-12 Benzim-idazole Ex. Inter- MS # mediate Amine Structure Compound Name MH+ 401 86

4-((2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-6- chloro-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile hydrochloride 384.0 402 95

(S)-4-((2-(3- aminopiperidin-1-yl)-6- methoxy-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile hydrochloride 362.0 403 95

4-((2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-6- methoxy-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 380.0 404 95

(S)-4-((2-(3- aminopiperidin-1-yl)-5- methoxy-3H-imidazo[4,5-b]pyridin-3- yl)methyl)benzonitrile hydrochloride 363.0 405 86

(R)-4-((2-(1-amino-4,4- difluoropiperidin-1-yl)-6- chloro-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 402.0 406 95

(R)-4-((2-(3-amino-4,4- difluoropiperidin-1-yl)-6- methoxy-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 398.0 407 92

(R)-4-((2-(3-amino-4,4- difluoropiperidin-1-yl)-4- chloro-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 402.0 408 97

4-((2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-4- chloro-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 384.0 409 92

4-((2-(3R,4S)-3-amino-4- fluoropiperidin-1-yl)-4- chloro-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 384.0 410 97

(R)-4-((2-(3-amino-4,4- difluoropiperidin-1-yl)-4- methoxy-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 398.0 411 97

4-((2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-4- methoxy-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile 380.2 412 90

4-((2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1H-imidazo[4,5-c]pyridin-1- yl)methyl)benzonitrile 351.2 413 91

4-((2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-3H-imidazo[4,5-c]pyridin-3- yl)methyl)benzonitrile 351.2 414 87

4-((2-((3R,4R)-3-amino-4- fluoro-1-piperidinyl)-6-ethoxy-1H-benzimidazol-1- yl)methyl)benzonitrile 394.2 415 88

4-((2-((3R,4S)-3-amino-4- fluoropiperidin-1-yl)-1H-imidazol[4,5-b]pyridin-1- yl)methyl)benzonitrile 351.2 416 89

4-((2-((3R)-3-amino-4,4- difluoro-1-piperidinyl)-6-fluoro-1H-benzimidazo-1- yl)methyl)benzonitrile 386.2 417 88

4-((2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-1H-imidazo[4,5-b]pyridin-1- yl)methyl)benzonitrile 351.2 418 92

(S)-4-((2-(3- aminopiperidin-1-yl)-4- chloro-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile 2,2,2-trifluoroacetate 366.0 419 93

(S)-4-((2-(3- aminopiperidin-1-yl)-3H- imidazo[4,5-b]pyridin-3-yl)methyl)benzonitrile hydrochloride 333.2 420 86

4-((2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6- chloro-1H-benzo[d]imidazol-1- yl)methyl)benzonitrile hydrochloride 384.2 421 86

(S)-4-((2-(3- aminopiperidin-1-yl)-6- chloro-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile 366.2 422 98

(S)-4-((2-(3- aminopiperidin-1-yl)-5- chloro-1H- benzo[d]imidazol-1-yl)methyl)benzonitrile 366.2

TABLE 9 Characterization data for compounds following Schemese 11-12.Ex. Freq., # Solvent ¹HNMR Data (δ ppm) 401 400 MHz 8.57 (br s, 2H),7.81-7.86 (m, 1H), 7.83 (d, J = 7.30 Hz, 1H), 7.50-7.55 (m, 1H), d₆-DMSO7.40-7.43 (m, 1H), 7.34-7.39 (m, 2H), 7.23 (dd, J = 1.92, 8.34 Hz, 1H),5.49-5.60 (m, 2H), 5.22-5.04 (m, 1H), 3.61-3.69 (m, 4H), 3.34-3.44 (m,4H), 3.22-3.31 (m, 1H), 3.08-3.22 (m, 1H), 2.05-2.16 (m, 1H), 1.93-2.05(m, 1H) 402 400 MHz 8.45 (br s, 3H), 7.87 (d, J = 8.29 Hz, 2H), 7.49 (t,J = 8.91 Hz, 3H), 6.95-7.02 (m, d₆-DMSO 2H), 5.56-5.72(m, 2H), 3.72 (s,3H), 3.37(br d, J = 7.67 Hz, 4H), 3.12 (br t, J = 10.05 Hz, 1H), 1.97(br d, J = 8.40 Hz, 1H), 1.88 (br dd, J = 3.63, 9.64 Hz, 1H), 1.62-1.70(m, 1H), 1.56 (br dd, J = 4.09, 9.38 Hz, 1H) 403 400 MHz 7.80 (d, J =8.29 Hz, 2H), 7.27-7.37 (m, 3H), 6.81 (d, J = 2.38 Hz, 1H), 6.73 (dd,d₆-DMSO J = 2.44, 8.66 Hz, 1H), 5.40 (s, 2.H), 4.66-4.87 (m, 1H), 3.68(s, 3H), 3.14-3.21 (m, 2H), 3.00-3.10 (m, 3H), 2.90-2.99 (M, 2H),1.81-2.03 (m, 2H) 404 400 MHz 8.40 (br s, 3H), 7.79-7.89 (m, 3H), 7.52(d, J = 7.98 Hz, 2H), 6.75 (d, J = 8.60 Hz, d₆-DMSO 1H), 5.45-5.59 (m,2H), 3.79 (s, 3H), 3.64-3.76 (m, 1H), 3.48 (br dd, J = 4.25, 11.30 Hz,2H), 3.21-3.31 (m, 1H), 3.00 (br t, J = 10.21 Hz, 1H), 1.93-2.02 (m 1H),1.80- 1.93 (m, 1H), 1.46-1.69 (m, 2H) 405 400 MHz 7.82 (d, J = 7.88 Hz,2H), 7.47 (d, J = 8.40 Hz, 1H), 7.29-7.35 (m, 3H), 7.14 (d, d₆-DMSO J =8.50 Hz, 1H), 5.49 (s, 2H), 3.26-3.40 (m, 2H), 3.08-3.24 (m, 2H),2.93-3.05 (m, 1H), 2.18-2.32 (m, 1H), 1.90-2.15 (m, 1H), 1.77 (br s, 2H)

Example 425:(3R,4R)-4-fluoro-1-(1-((5-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine

Step 1, tert-Butyl((3R,4R)-4-fluoro-1-(1-(methylsulfonyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-yl)carbamate

tert-Butyl((3R,4R)-1-(1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(Intermediate 54, 156 mg, 0.467 mmol) was dissolved in DCM (2.3 mL). Themixture was treated with methanesulfonyl chloride (100 μl, 0.700 mmol, 2equiv) and triethylamine, anhydrous (197 μl. 1.400 mmol). The resultingyellow solution was left to stir overnight. The reaction was quenchedwith NH₄Cl (aq), diluted with DCM, extracted into DCM, dried over MgSO₄,filtered, concentrated to give the crude as an oil. The oil was purifiedon column chromatography (25 g SiO2, 0-45% ethyl acetate in heptane), togive tert-butyl((3R,4R)-4-fluoro-1-(1-(methylsulfonyl)-H-benzo[d]imidazol-2-yl)piperidin-3-yl)carbamateas a colorless solid. (ESI, pos. ion) m/z: 413.2 [M+1].

Step 2. Tert-butyl((3R,4R)-4-fluoro-1-(1-((5-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-yl)carbamate

A vial was charged with(S)-1-(1-(methylsulfonyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine(150 mg, 0.38 mmol), 1-hydroxy-2,3-dihydro-1H-indene-5-carbonitrile (67mg, 1.1 equiv), and Cs₂CO₃ (150 mg, 1.2 equiv). The vial was fitted witha stirring bar, capped, and MeCN (1.3 ml) was added. The mixture wasplaced into a heating block set at 90(C for 18 h. The reaction wasdiluted with EtOAc and NH₄Cl_((aq)), the mixture was extracted intoEtOAc. The combined organic extracts were dried over MgSO4, filtered,and concentrated to give the reaction crude. Crude material was purifiedon column chromatography (4 g SiO₂, 0-30% EtOAc in heptane) to affordtert-butyl ((3R,4R)-4-fluoro-1-(1-((5-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-yl)carbamateas a colorless oil. (ESI, pos. ion) m/z: 456.2 [M+1].

Step 3.(3R,4R)-4-fluoro-1-(1-((5-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine(Example 425)

tert-butyl((3R,4R)-4-fluoro-1-(1-((5-methoxypyridin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-yl)carbamate(32 mg, 1 equiv) was dissolved in DCM (5 mL). HCl in dioxane (10 equiv)was added, and the mixture was allowed to stir overnight. The solutionwas concentrated, then purified using reverse phase HPLC to provide thetitle compound. ¹H NMR (600 MHz, d₆-DMSO) δ 7.79 (s, 1H), 7.50 (t,J=7.53 Hz, 2H), 7.11 (t, J=7.66 Hz. 1H), 6.96 (d, J=7.79 Hz, 1H).6.88-6.94 (m, 1H), 6.39-6.49 (m, 1H), 6.19 (t, J=8.95 Hz, 1H), 3.54-3.62(m, 1H), 3.36-3.43 (m, 1H), 3.18-3.24 (m, 3H), 3.00-3.13 (m, 2H).2.74-2.87 (m, 1H), 2.52-2.63 (m, 1H), 1.91-2.12 (m, 2H), 1.77-1.89 (m,1H), 1.47-1.56 (m, 1H). (ESI, pos. ion) m/z: 356.2 [M+1].

TABLE 10 Compounds made following Scheme 13 and analogous to preparationof Example 425 MS Ex. # Alcohol Structure Compound Name MH+ 423

(R)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)-2,3-dihydro-1H- indene-5-carbonitrile 358.2 424

(S)-1-(2-((S)-3- aminopiperidin-1-yl)- 1H-benzo[d]imidazol-1-yl)-2,3-dihydro-1H- indene-5-carbonitrile 358.2 425

(3R,4R)-4-fluoro-1-(1- ((5-methoxypyridin-2- yl)methyl)-1H-benzo[d]imidazol-2- yl)piperidin-3-amine 356.2

TABLE 11 Characterization data for compounds made following scheme 13SFC Isomer Ex. Freq., Separation Separation # Solvent ¹HNMR Data (δ ppm)Stage Conditions 423 500 MHz 7.79 (s, 1H), 7.50 (t, J = 7.53 Hz, 2H),7.11 (t, J = 7.66 B Phenomenex d₄-MeOH Hz, 1H), 6.96 (d, J = 7.79 Hz,1H), 6.88-6.94 (m, Lux Cellulose-2, 1H), 6.39-6.49 (m, 1H), 6.19 (t, J =8.95 Hz, 1H), 30% MeOH, 3.54-3.62 (m, 1H), 3.36-3.43 (m, 1H), 3.18-3.24(m, Chiralcel OD, 3H), 3.00-3.13 (m, 2H), 2.74-2.87 (m, 1H), 2.52- 25%MeOH 2.63 (m, 1H), 1.91-2.12 (m, 2H), 1.77-1.89 (m, 1H), Peak 11.47-1.56 (m, 1H) 424 500 MHz 7.79 (s, 1H), 7.49 (dd, J = 7.91, 11.03Hz, 2H), 7.06- B Phenomenex d₄-MeOH 7.14 (m, 1H), 6.86-6.96 (m, 2H),6.45 (br d, J = 5.71 Lux Cellulose-2, Hz, 1H), 6.19 (br t, J = 8.95 Hz,1H), 3.53-3.62 (m, 30% MeOH, 1H), 3.35-3.44 (m, 2H), 3.11-3.24 (m, 3H),2.81- Peak 3 2.96 (m, 2H), 2.51-2.65 (m, 1H), 1.90-2.10 (m, 2H),1.73-1.88 (m, 1H), 1.42-1.53 (m, 1H) 425 600 MHz, 8.22 (d, J = 2.80 Hz,1H), 7.42 (d, J = 7.79 Hz, 1H), — — d₆-DMSO 7.37 (dd, J = 3.11, 8.72 Hz,1H), 7.17 (d, J = 8.72 Hz, 1H), 7.11 (d, J = 7.79 Hz, 1H), 7.04-7.09 (m,1H), 6.98-7.03 (m, 1H), 5.31 (s, 2H), 4.32-4.47 (m, 1H), 3.79 (s, 3H),3.40-3.52 (m, 2H), 2.96-3.09 (m, 2H), 2.84 (dd, J = 8.72, 12.46 Hz, 1H),2.04-2.14 (m, 1H), 1.73-1.84 (m, 1H)

Example 426:1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)azetidine-3-carbonitrile

Step 1. methyl2-(2-((3R,4R)-3-((tert-butoycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluor-1H-benzo[d]imidazol-1-yl)acetate

A vial was charged with tert-butyl((3R,4R)-1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(0.3 g, 0.810 mmol) Cs₂CO₃ (0.792 g, 2.430 mmol) in acetonitrile (2.70ml), and methyl 2-bromoacetate (0.149 g, 0.972 mmol) and shaken on J-Kemblock for 16 h. Reaction mixture was filtered through Celite® brandfilter agent plug and purified by reverse phase HPLC to obtain methyl2-(2-((3R,4R)-3-((tert-butoxycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetate.¹H NMR (600 MHz. DMSO-d₆) δ 7.56 (t, J=9.06 Hz, 1H), 7.51 (t, J=8.85 Hz,1H). 7.19 (br d. J=8.25 Hz, 1H), 4.94-5.03 (m, 2H). 4.51-4.59 (dt.J=4.63, 9.01 Hz, 1H), 3.68-3.77 (m, 3H), 3.35-3.46 (m, 2H). 3.24-3.30(m, 1H). 2.95 (br t. J=10.63 Hz. 1H), 2.73-2.89 (m, 1H), 2.13-2.21 (m,1H), 1.79-1.89 (m, 1H), 1.39 (s, 911). MS: (ESI pos. ion) m z: 443.2[M+1].

Step 2.2-(2-((3R,4R)-3-((tert-butoxycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluoro-H-benzo[d]imidazol-1-yl)aceticacid

Methyl2-(2-((3R,4R)-3-((tert-butoxycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetatewas saponified using LiOH (0.097 g, 4.05 mmol) in dioxane (1 mL) andwater (1 mL). Reaction mixture was stirred at ambient temperature for 1h. Reaction mixture was acidified using acetic acid and the resultingoff white precipitate was filtered to obtain2-(2-((3R,4R)-3-((tert-butoxycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)aceticacid. MS: (ESI pos. ion) m/z: 429.2 [M+1].

Step 3, tert-butyl((3R,4R)-1-(1-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)-5,6-difluoro-H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate

A solution of2-(2-((3R,4R)-3-((tert-butoxycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)aceticacid (0.015 g, 0.035 mmol). 3-cyanoazetidine hydrochloride (4.15 mg.0.035 mmol) and 2-(1h-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexaflurophosphate (0.013 g, 0.035 mmol) in dimethyl sulfoxide (0.117mil) and DIPEA (0.024 ml, 0.140 mmol) was shaken at ambient temperature.The reaction mixture was purified by reverse phase HPLC to obtaintert-butyl((3R,4R)-1-(1-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate.MS: (ESI pos. ion) m/z: 493.2 [M+1].

Step 4.1-(2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)acetyl)azetidine-3-carbonitrile(Example 426)

tert-Butyl((3R,4R)-1-(1-(2-(3-cyanoazetidin-1-yl)-2-oxoethyl)-5,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamatewas treated with TFA (0.5 mL) in DCM (0.5 mL). Mixture was concentratedand purified using reverse phase HPLC to obtain the title compound. ¹HNMR (600 MHz, DMSO-d₆) δ 7.34-7.60 (m, 2H), 4.73-4.80 (m, 2H), 4.48-4.60(m, 2H), 4.31-4.48 (m, 1H). 4.17-4.28 (m, 1H), 4.06-4.15 (m, 1H),3.82-3.94 (m, 1H), 2.96-3.06 (m, 2H). 2.74-2.84 (m, 1H), 2.06-2.17 (m,1H), 1.64-1.88 (m, 3H). MS: (ESI pos. ion) m/z: 393.2 [M+1].

The following compounds were made following an analogous procedure tothat described for Example 426 and general Scheme 14 above:

TABLE 12 Compounds made following Scheme 14 MS Ex. # Amine StructureCompound Name MH+ 426

1-(2-(2-((3R.,4R)-3- amino-4- fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)azetidine-3- carbonitrile 393.2 427

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(3-(tert- butoxy)azetidin-1- yl)ethan-1-one440.2 428

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(3,3-difluoroazetidin- 1-yl)ethanone 404.2 429

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(3-isopropylazetidin- 1-yl)ethanone 410.2 430

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(6,6-difluoro-2- azaspiro[3.3]heptan-2-yl)ethanone 444.2 431

2-(2-((3R,4R)-3-amino- 4-fluoropiperidin-1-yl)- 5,6-difluoro-1H-benzo[d]imidazol-1-yl)- 1-(7-oxa-2- azaspiro[3.5]nonan-2- yl)ethanone438.2

TABLE 13 Characterization data for compounds made following scheme 14SFC Isomer Ex. Freq., Separation Separation # Solvent ¹HNMR Data (δ ppm)Stage Conditions 426 600 MHz, 7.34-7.60 (m, 2H), 4.73-4.80 (m, 2H),4.48-4.60 (m, — — DMSO-d₆ 2H), 4.31-4.48 (m, 1H), 4.17-4.28 (m, 1H),4.06-4.15 (m, 1H), 3.82-3.94 (m, 1H), 2.96-3.06 (m, 2H), 2.74- 2.84 (m,1H), 2.06-2.17 (m, 1H), 1.64-1.88 (m, 3H), 427 600 MHz, 7.46 (dd, J =7.43, 11.17 Hz, 1H), 7.40 (dd, J = 7.36, — — DMSO-d₆ 10.39 Hz, 1H),4.72-4.79 (m, 2H), 4.56-4.64 (m, 1H), 4.41-4.49 (m, 2H), 4.36 (br s,1H), 4.16 (dd, J = 7.20, 9.77 Hz, 3H), 4.08 (dt, J = 4.98, 8.25 Hz, 1H),3.70 (dd, J = 4.71, 10.00 Hz, 1H), 2.95-3.06 (m, 2H), 2.78 (ddd, J =5.02, 8.10, 12.73 Hz, 1H), 2.02-2.16 (m, 1H), 1.89 (br s, 1H), 1.72-1.87(m, 1H), 1.15 (s, 9H), 428 600 MHz, 7.37-7.50 (m, 2H), 4.87 (s, 1H),4.76-4.85 (m, 2H), — — DMSO-d₆ 4.34-4.47 (m, 2H), 3.20-3.27 (m, 1H),3.14-3.19 (m, 1H), 2.98-3.11 (m, 2H), 2.87-2.97 (m, 1H), 2.79 (dd, J =8.37, 12.57 Hz, 1H), 2.03-2.18 (m, 1H), 1.96 (dt, J = 4.67, 9.19 Hz,1H), 1.78-1.91 (m, 1H) 429 600 MHz, 7.46 (dd, J = 7.47, 11.13 Hz, 1H),7.38 (dd, J = 7.32, — — DMSO-d₆ 10.67 Hz, 1H), 4.70-4.79 (m, 2H),4.32-4.47 (m, 1H), 4.25-4.30 (m, 1H), 3.92-3.99 (m, 2H), 3.62 (dd, J =5.92, 9.65 Hz, 1H), 3.34-3.43 (m, 1H), 2.96-3.05 (m, 2H), 2.76-2.82 (m,1H), 2.31-2.47 (m, 1H), 2.08- 2.16 (m, 1H), 1.74-1.91 (m, 3H), 0.86 (t,J = 5.57 Hz, 6H) 430 600 MHz, 7.47 (t, J = 9.20 Hz, 1H), 7.39 (dd, J =7.36, 10.70 Hz, — — DMSO-d₆ 1H), 4.74 (d, J = 1.79 Hz, 2H), 4.32-4.46(m, 3H), 4.03-4.10 (m, 2H), 3.37-3.54 (m, 1H), 2.92-3.05 (m, 3H), 2.88(t, J = 12.38 Hz, 4H), 2.74-2.83 (m, 1H), 2.11 (ddd, J = 3.97,8.10,17.13 Hz, 1H), 1.74-1.93 (m, 1H), 431 600 MHz, 7.47 (dd, J = 7.43,11.17 Hz, 1H), 7.39 (dd, J = 7.36, — — DMSO-d₆ 10.70 Hz, 1H), 4.72-4.80(m, 2H), 4.34-4.47 (m, 1H), 4.02 (q, J = 8.33 Hz, 2H), 3.69 (s, 2H),3.46-3.59 (m, 4H), 3.34-3.36 (m, 1H), 2.96-3.06 (m, 2H), 2.80 (dd, J =8.21, 12.50 Hz, 1H), 2.08-2.16 (m, 1H), 1.70- 1.88 (m, 6H)

Example 432:(R)-6-((2-(4,4-difluoro-3-(methylamino)piperidin-1-yl)-6-fluoro-H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

A vial was charged with(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(100 mg. 0.259 mmol). The vial was fitted with a stirring bar and DMF(1.3 mL) was added. Potassium carbonate (53.7 mg. 0.388 mmol) was added,followed by iodomethane (40.4 mg, 0.285 mmol). The mixture was left tostir at room temperature for 2 hours. Formation of the mono andbis-methylated amine was observed by LCMS. The reaction was worked up bydiluting with EtOAc and NH₄Cl (aq). The mixture was extracted withEtOAc, the organic extracts were combined, dried over MgSO₄, filteredand concentrated to give the crude mixture. The crude was purified onHPLC to afford the title compound. MS: (ESI pos. ion) m/z: 401.2 [M+1];¹H NMR (600 MHz, d₆-DMSO) δ 8.95 (dd, J=0.62, 2.18 Hz, 1H), 8.33 (dd.J=2.18, 8.10 Hz. 1H). 7.51 (d. J=8.10 Hz. 1H). 7.46 (dd, J=4.98, 8.72Hz, 1H), 7.11 (dd. J=2.49, 9.03 Hz. 1H). 6.95 (ddd, J=2.49, 8.72, 9.96Hz, 1H), 5.54 (s, 2H), 3.35-3.41 (m, 1H), 3.28-3.32 (m, 1H), 3.10-3.16(m, 1H), 2.91-2.96 (m, 1H). 2.88 (td, J=3.66, 13.23 Hz, 1H). 2.25 (s,3H), 2.13-2.23 (m, 1H), 2.01-2.13 (m, 1H).

Example 433:(R)-1-((2-(4,4-difluoro-3-((2-hydroxyethyl)amino)piperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

Step 1.(R)-6-((2-(3-((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile

(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(89.4 mg, 0.231 mmol) was combined with(tert-butyldimethylsilyloxy)acetaldehyde (63.7 μl. 0.301 mmol) in avial. Tetrahydrofuran (2.3 mL) and sodium cyanoborohydride (24.2 μl,0.463 mmol) were added. The mixture was allowed to stir at roomtemperature for 2 hours, at which time starting material was fullyconsumed. The reaction was quenched with NH₄Cl(aq), extracted intoEtOAc, washed with brine, dried over MgSO₄, filtered and concentrated togive(R)-6-((2-(3-((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile,which was used in the next step without further purification.

Step 2.(R)-6-((2-(4,4-difluoro-3-((2-hydroxyethyl)amino)piperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(Example 433)

(R)-6-((2-(3-((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrilewas dissolved in THF (2.3 mL), and tetrabutylammonium fluoride (1.0 Msolution in THF, 301 μl. 0.301 mmol) was added. The mixture was left tostir at rt for 16 h. Clean deprotection was observed by LCMS. Theresulting mixture was worked up by diluting with water and EtOAc,extracting into EtOAc, drying over MgSO₄, filtering and concentrating.The crude was purified by column chromatography (4 g SiO₂, 0-70% EtOAcin heptane) to furnish the title compound. MS: (ESI pos. ion) m/z: 431.2[M+1]. ¹H NMR (500 MHz, d₄-MeOH) δ 8.82 (br s, 1H). 8.13-8.25 (m, 1H).7.59 (d, J=8.30 Hz, 1H), 7.55 (dd, J=4.67, 8.30 Hz, 1H), 6.98-7.06 (m,2H). 5.58 (s, 2H). 4.17 (did, J=4.80, 8.63, 12.98 Hz, 1H), 4.06 (br d.J=13.23 Hz, 1H), 3.84-3.95 (m, 2H), 3.53-3.66 (m, 2H), 3.38-3.47 (m,1H), 3.32-3.37 (m, 2H), 2.25-2.42 (m, 2H).

Example 434:(S)-6-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinicacid

A vial was charged with(S)-6-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(0.03 g, 0.09 mmol) and 3.99 N aqueous hydrochloric acid (0.075 ml,0.451 mmol) in 1,4-dioxane (0.301 ml), and shaken at ambient temperaturefor 1 h. The reaction mixture was concentrated and purified by reversephase HPLC. ¹H NMR (600 MHz, DMSO-d₆) δ 13.23-13.65 (br s, 1H), 8.98 (d,J=1.40 Hz, 1H), 8.29 (br d, J=6.85 Hz. 1H). 8.12-8.19 (m, 1H), 8.11 (brs, 1H), 7.51 (br d, J=7.71 Hz, 1H), 7.21 (br s, 1H). 7.15 (br s, 1H),5.57-5.61 (br s, 2H). 3.58-3.76 (m, 1H). 3.44-3.57 (m, 1H). 3.16-3.29(m. 2H). 3.06 (br s, 1H), 2.52-2.55 (m, 1H), 1.95 (br s, 1H), 1.83 (brs, 1H), 1.53-1.64 (m, 1H). MS: (ESI pos. ion) m/z: 352.2 [M+I].

Example 435:(S)-6-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinamide

A vial containing(S)-6-((2-(3-aminopiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(0.03 g. 0.090 mmol) and NaOH (1 M in water) (0.271 ml. 0.271 mmol) inmethanol (0.30 mL) was shaken at rt for 3 h. The reaction mixture wasdiluted with EtOAc, filtered, concentrated, and purified by reversephase HPLC to afford the title compound. ¹H NMR (600 MHz, DMSO-d₆) δ8.94 (s, 1H). 8.16 (dd, J=2.22, 8.14 Hz, 1H). 8.11 (br s, 1H), 7.56 (brs, 1H), 7.43 (d, J=7.79 Hz, 1H), 7.18 (d, J=8.17 Hz. 1H), 6.98-7.11 (m,3H). 5.38-5.44 (m, 2H), 3.37-3.43 (m, 1H), 2.76-2.89 (m, 2H). 2.57-2.66(m, 1H), 2.52-2.56 (m, 1H), 1.78-1.84 (m, 1H). 1.65-1.74 (m, 1H),1.50-1.58 (m, 1H). 1.14-1.28 (m, 1H). MS: (ESI pos. ion) m/z: 351.2[M+1].

Example 436:6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinamide

A vial containing6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile(0.03 g, 0.090 mmol) and NaOH (1 M in water) (0.271 ml, 0.271 mmol) inmethanol (0.301 ml) was shaken at ambient temperature for 3 h. Thereaction mixture was diluted with EtOAc, filtered concentrated andpurified by reverse phase HPLC to afford the title compound. ¹H NMR (500MHz. MeOH-d4) δ 8.84-9.04 (m, 1H), 8.08-8.27 (m, 1H), 7.48-7.58 (m, 1H).7.06-7.34 (m, 4H), 5.51 (br d, J=6.75 Hz, 3H), 4.29-4.50 (m, 1H), 3.61(br dd, J=3.89, 7.79 Hz. 1H), 3.39-3.50 (m, 1H), 2.87-3.19 (m, 3H).2.10-2.27 (m, 1H). 1.78-1.97 (m, 1H), 0.79-0.98 (m, 1H). MS: (ESI pos.ion) m/z: 369.2 [M+11].

Example 437:2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)aceticacid

2-(2-((3R,4R)-3-((tert-butoxycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)aceticacid was treated with TFA (0.5 mL) in DCM (1 mL) and stirred at rt for 1h. Reaction mixture was concentrated and purified via reverse phase HPLCto obtain the title compound. ¹H NMR (600 MHz, DMSO-d6) δ 7.47-7.60 (m,2H), 4.82-4.92 (m, 2H), 4.51-4.59 (dt. J=4.63, 9.01 Hz, 1H), 3.35-3.46(m, 2H), 3.24-3.30 (m, 1H), 2.95 (br t, J=10.63 Hz, 1H). 2.73-2.89 (m,1H), 2.13-2.21 (m, 1H), 1.79-1.89 (m, 1H). MS: (ESI pos. ion) m/z: 329.0[M+1].

Examples 438-441:6-((R)-1-(4,6-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 596) and6-((S)-1-(4,6-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 597) and6-((R)-1-(5,7-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 598) and6-((S)-1-(5,7-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 599)

Step 1, tert-butyl((3R,4R)-1-(1-(1-(5-cyanopyridin-2-yl)ethyl)-4,6-difluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-yl)carbamate(1.05 g. 2.098 mmol, mixture of 4 isomers) and methyl iodide (0.144 ml,2.308 mmol) were dissolved in THF and cooled to 0 C. potassiumbis(trimethylsilyl)amide solution, 1m in tetrahydrofuran (2.203 ml,2.203 mmol) was added slowly and the reaction stirred for 1 hour.Conversion stalled, so the reaction was quenched with ammonium chloride,then extracted with DCM (3×). The organics were combined, dried overNa2SO4, filtered, and concentrated to provide a mixture of methylatedand N—H products.

Step 2. Isomers were separated using chiral SFC: Chiralpak Cel2, 15%MeOH, 0.2% DEA.

Step 3. Each individual isomer (100 mg. 1 equiv), was dissolved in DCM(5 mL), then TFA (0.5 mL) was added. After 1 hour, the solutions werepoured onto pre-wetted SCX columns and flushed with methanol. Theproducts were eluted with methanolic ammonia.

Peak 1:6-((R)-1-(4,6-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 438)

¹H NMR (500 MHz, METHANOL-d4) δ ppm 1.88-2.08 (m, 4H) 2.22-2.33 (m, 1H)2.41-2.50 (m, 3H) 2.99 (dd, J=12.72, 9.34 Hz, 1H) 3.16-3.30 (m, 2H)3.50-3.64 (m, 1H) 3.77-3.95 (m, 1H) 4.53-4.76 (m, 1H) 5.97 (q, J=7.01Hz, 1H) 6.63-6.78 (m, 1H) 7.04-7.16 (m, 1H) 7.62 (d, J=8.30 Hz, 1H) 8.19(dd, J=8.30, 2.08 Hz, 1H) 8.84 (d, J=1.56 Hz, 1H). MS: (ESI pos. ion)m/z: 415.2 [M+1].

Peak 2:6-((S)-1-(4,6-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 597)

¹H NMR (500 MHz, METHANOL-d4) δ ppm 1.97 (d. J=7.01 Hz. 3H) 2.03-2.28(m, 2H) 2.52 (s, 3H) 2.99-3.21 (m, 3H) 3.59 (br d, J=12.98 Hz, 1H)3.71-3.80 (m, 1H) 4.54-4.75 (m, 1H) 5.97 (q, J=7.01 Hz, 1H) 6.64-6.75(m, 1H) 7.10 (dd, J=8.82, 2.08 Hz, 1H) 7.58 (d, J=8.30 Hz, 1H) 8.18 (dd,J=8.30, 2.08 Hz, 1H) 8.76-8.87 (m. 1H). MS: (ESI pos. ion) m: 415.2[M+1].

Peak 3:6-((R)-1-(5,7-difluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 598)

¹H NMR (500 MHz, METHANOL-d4) δ ppm 2.01 (d, J=7.27 Hz. 4H) 2.18-2.33(m, 1H) 2.49 (s, 3H) 2.98 (dd. J=12.46, 9.34 Hz, 1H) 3.14-3.28 (m, 2H)3.47 (br dd, J=12.85, 1.95 Hz, 1H) 3.79 (dtd, J=8.40, 4.04, 4.04, 2.47Hz, 1H) 4.57-4.76 (m, 1H) 5.91-6.04 (m, 1H) 6.67-6.85 (m, 2H) 7.63 (d,J=8.30 Hz, 1H) 8.13-8.25 (m, 1H) 8.84-8.96 (m, 1H). MS: (ESI pos. ion)m/n: 415.2 [M+1].

Peak 4:6-((S)-1-(5,7-difluo-2-((3R,4R)-4-fluoro-2-((3R,4R)-4-fluoro-3-(methylamino)piperidin-1-yl)-1H-benzo[d]imidazol-1-yl)ethyl)nicotinonitrile(Example 599)

¹H NMR (500 MHz, METHANOL-d4) δ ppm 2.02 (d, J=7.01 Hz, 3H) 2.16-2.35(m, 1H) 2.51-2.68 (m, 3H) 2.98-3.20 (m, 3H) 3.46-3.60 (m, 1H) 3.65-3.78(m, 1H) 4.54-4.78 (m, 1H) 5.99 (q. J=7.27 Hz, 1H) 6.64-6.85 (m, 2H) 7.58(d. J=8.30 Hz, 1H) 8.19 (dd, J=8.17, 2.21 Hz, 1H) 8.83-8.96 (m, 1H). MS:(ESI pos. ion) m/z: 415.2 [M+1].

Example 607:2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-((1R,5S)-3-azabicyclo[3.1.0]hexan-3-yl)ethanone

Step 1.2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-1-((1R,5S)-3-azabicyclo[3.1.0]hexan-3-yl)ethanone

2-(2-((3R,4R)-3-((tert-butoxycarbonyl)amino)-4-fluoropiperidin-1-yl)-5,6-difluoro-H-benzo[d]imidazol-1-yl)aceticacid (110 mg, 0.257 mmol), 1,1′-dimethyltriethylamine (135 μl, 0.770mmol), and tetrahydrofuran (1284 μl) were combined in a vial and cooledto 0 C, trimethyl acetyl chloride (24.12 μl, 0.282 mmol) was addeddropwise and the mixture stirred for 15 minutes. LCMS showed fullconversion to mixed anhydride (appears as methyl ester by LCMS from MeOHdisplacement). 3-azabicyclo[3.1.0]hexane (1.5 equiv) was added andallowed to stir for 1 hour. The mixture was concentrated down, thenredissolved in DCM/TFA (1:1) and allowed to stir for 1 hour. The mixturewas reconcentrated, then redissolved in 1 mL DMSO, filtered, andpurified by reverse phase HPLC to provide the desired product.

TABLE 14 The following compounds were made following an analogousprocedure to that described for Example 607 and general Scheme 15 above:Boc Ex. Deprotection MS # Amine Procedure Structure Compound Name MH+600

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(2- methylazetidin-1- yl)ethanone 382.0 601

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (2,2-difluoroethyl)-N- methylacetamide 406.2602

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- cyclopropyl-N- methylacetamide 382.2 603

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- ((R)-1-cyanoethyl)-N- methylacetamide 395.2604

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-((R)-1-pyridin-2- yl)ethyl)acetamide447.0 605

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- ethyl-N-methylacetamide 370.2 606

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (2-fluoroethyl)-N- methylacetamide 388.2 607

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1- ((1R,5S)-3- azabicyclo[3.1.0]hexan-3-yl)ethanone 394.0 608

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-(1-(pyridin-2- yl)ethyl)acetamide447.2 609

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(2- azabicyclo[3.1.0]hexan-2- yl)ethanone 394.2610

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- ((S)-1-cyanoethyl)-N- methylacetamide 395.4611

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-(tetrahydrofuran- 3-yl)acetamide412.2 612

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (1-cyanopropan-2-yl)-N- methylacetamide 409.2613

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-(1-(pyridin-4- yl)ethyl)acetamide447.2 614

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-(1,1,1- trifluoropropan-2-yl)acetamide 438.2 615

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (cyanomethyl)-N- methylacetamide 381.2 616

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-propylacetamide 384.2 617

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- cyclopropyl-N-(2- hydroxyethyl)acetamide 412.0618

B

1-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-3- fluoropyrrolidine-3- carbonitrile425.2 619

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(2- oxa-5- azabicyclo[2.2.1]heptan-5-yl)ethanone 410.0 620

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1- (hexahydropyrano[4,3- b][1,4]oxazin-4(7H)-yl)ethanone 454.2 621

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (2-cyanopropyl)-N- methylacetamide 409.2 622

B

-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-(3,3,3- trifluoropropyl)acetamide438.2 623

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1- ((1R,5S)-6,6-difluoro-3-azabicyclo[3.1.0]hexan-3- yl)ethanone 430.2 624

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(4- (pyrimidin-2-yl)piperazin-1- yl)ethanone475.0 625

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(2- isopropylazetidin-1- yl)ethanone 410.2 626

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(3- (difluoromethoxy)pyrrolidin- 1-yl)ethanone448.2 627

B

4-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)morpholine-2- carbonitrile 423.0 628

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(3- hydroxypiperidin-1- yl)ethanone 412.2 629

B

1-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-4- methylpiperidine-4- carbonitrile 435.2630

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1- (3,4-dihydro-1,8- naphthyridin-1(2H)-yl)ethanone 445.0 631

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- cyclopropyl-N-(2,2- difluoroethyl)acetamide432.2 632

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1- (5H-pyrrolo[3,4-b]pyridin- 6(7H)-yl)ethanone431.2 633

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-((tetrahydrofuran-3-yl)methyl)acetamide 426.0 634

B

-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (2,2-difluoroethyl)-N- methylacetamide 406.2635

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyl-N-(2,2,2- trifluoroethyl)acetamide424.2 636

B

(R)-1-(2-(2-((3R,4R)-3- amino-4-fluoropiperidin-1- yl)-5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)pyrrolidine-2- carbonitrile 407.0 637

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- ((1r,4R)-4- hydroxycyclohexyl)-N-methylacetamide 440.0 638

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- methyi-N-((S)-1-(pyridin-2- yl)ethyl)acetamide447.2 639

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1- (octahydro-1H-pyrano[4,3-b]pyridin-1-yl)ethanone 452.2 640

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(4- hydroxypiperidin-1- yl)ethanone 412.2 641

B

1-(3-(1H-1,2,4-triazol-1- yl)azetidin-1-yl)-2-(2- ((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-5,6- difluoro-1H- benzo[d]imidazol-1- yl)ethanone435.2 642

B

7-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)hexahydroimidazo [1,5-a]pyrazin-3(2H)-one452.2 643

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (2-cyanoethyl)-N- ((tetrahydrofuran-3-yl)methyl)acetamide 465.2 644

B

4-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-N- methylmorpholine-2- carboxamide 455.2645

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(3- ((methylsulfonyl)methyl)pyrrolidin-1-yl)ethanone 474.2 646

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1- (5,6-dihydro- [1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)ethanone 435.2 647

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(2- (methoxymethyl)morpholino) ethanone 442.2648

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(3- hydroxy-3-methylpyrrolidin- 1-yl)ethanone412.2 649

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-1-(4- (methylsulfonyl)piperazin-1- yl)ethanone475.2 650

B

N-((1-acetylpyrrolidin-3- yl)methyl)-2-(2-((3R,4R)-3-amino-4-fluoropiperidin-1- yl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-N- ethylacetamide 481.2 651

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (1,1-dioxidotetrahydro-2H- thiopyran-4-yl)-N-methylacetamide 474.2 652

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- ((1,1- dioxidotetrahydrothiophen-3-yl)methyl)-N- methylacetamide 474.0 653

B

2-(1-(2-(2-((3R,4R)-3- amino-4-fluoropiperidin-1- yl)-5,6-difluoro-1H-benzo[d]imidazol-1- yl)acetyl)piperidin-4-yl)-2- methylpropanenitrile463.0 654

B

1-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-N- methylpiperidine-3- carboxamide 453.2655

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (2-hydroxyethyl)-N- (pyridin-3-ylmethyl)acetamide 463.2 656

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1-yl)-N- (2-cyanoethyl)-N- ttetrahydro-2H-pyran-4-yl)acetamide 465.2 657

B

1-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-N,N- dimethylpiperidine-3- carboxamide467.2 658

B

1-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)-4- (methoxymethyl)piperidine-4-carbonitrile 465.2 659

B

7-(2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-5,6- difluoro-1H-benzo[d]imidazol-1- yl)acetyl)tetrahydro-1H- oxazolo[3,4-a]pyrazin-3(5H)-one 453.2 660

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-(thiazol-2- yl)acetamide 393.0 661

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-(2,2,2- trifluoroethyl)acetamide392.2 662

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-cyclopropyl-N- (2,2,2-trifluoroethyl)acetamide 432.2 663

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-(2-methoxyethyl)-N- methylacetamide382.2 664

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-methyl-N-((S)- tetrahydrofuran-3-yl)acetamide 394.2 665

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-methyl-N-((R)- tetrahydrofuran-3-yl)acetamide 394.2 666

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((S)-1-(pyridin-2-yl)ethyl)acetamide 415.2 667

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((S)- tetrahydrofuran-3-yl)-N-(2,2,2- trifluoroethyl)acetamide 462.2 668

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-cyclobutylacetamide 364.2 669

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((S)-1-cyanopropan- 2-yl)acetamide377.2 670

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((R)-1-cyanopropan- 2-yl)acetamide377.2 671

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-ethyl-N-(2- methoxyethyl)acetamide396.2 672

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((R- tetrahydrofuran-3-yl)-N-(2,2,2- trifluoroethyl)acetamide 462.2 673

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-(3,3,3- trifluoropropyl)acetamide406.2 674

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((R)-1-(pyridin-2-yl)ethyl)acetamide 415.2 675

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((S)- tetrahydrofuran-3-yl)acetamide 380.2 676

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-N-((R)- tetrahydrofuran-3-yl)acetamide 380.2 677

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-(2-methylazetidin-1- yl)ethan-1-one464.2 678

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-((S)-3- methylmorpholino)ethan-1-one 394.2 679

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-((R)-3- methylpyrrolidin-1-yl)ethan-1-one 378.2 680

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-((R)-3- (methoxymethyl)morpholino)ethan-1-one 424.2 681

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-((R)-3- methylmorpholino)ethan-1-one 394.2 682

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-((S)-2- methylpyrrolidin-1-yl)ethan-1-one 378.2 683

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-(3,5- dimethylmorpholino)ethan-1-one 408.2 684

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-(3- ethylmorpholino)ethan-1- one408.2 685

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-((S)-3- cyclopropylmorpholino)ethan-1-one 420.2 686

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-((R)-3- (hydroxymethyl)morpholino)ethan-1-one 410.2 687

B

2-(2-((3R,4R)-3-amino-4- fluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol- 1-yl)-1-(3,3- dimethylmorpholino)ethan-1-one 408.2

TABLE 15 Characterization data for compounds tabulated in Table 14 8.The column “Separation Stage” indicates alter which process stepregioisomers formed due to asymmetric benzimidazole substitution at R¹in Scheme 15 were separated during the preparation of the tabulatedfinal compound (I = after preparation of the acetic acid intermediate(where at least one R¹ is not hydrogen); B = prior to boc deprotectionor F = final compound), SFC Isomer Ex. Freq., Separation Separation #Solvent ¹HNMR Data (δ ppm) Stage Conditions 600 600 MHz, 7.42-7.56 (m,1H), 7.38 (dd, J = 7.47, 10.59 Hz, — — DMSO- 1H), 4.60-4.88 (m, 2H),4.55-4.90 (m, 3H), 4.32- d6 4.52 (m, 2H), 4.11-4.21 (m, 1H), 3.76-3.90(m, 1H), 2.96-3.09 (m, 2H), 2.71-2.88 (m, 1H), 2.37- 2.46 (m, 1H), 2.12(dt, J = 3.11, 13.08 Hz, 1H), 1.73-1.90 (m, 3H), 1.53 (d, J = 6.23 Hz,1H), 1.35 (dd, J = 1.87, 6.23 Hz, 2H) 601 600 MHz, 7.44-7.53 (m, 1H),7.25-7.43 (m, 1H), 6.02-6.55 — — DMSO- (m, 1H), 4.99-5.11 (m, 2H),4.30-4.48 (m, 1H), d6 3.93-4.03 (m, 1H), 3.78 (dt, J = 3.74, 15.41 Hz,1H), 3.22 (s, 2H), 2.94-3.04 (m, 3H), 2.71-2.82 (m, 1H), 2.01-2.15 (m,1H), 1.70-1.87 (m, 3H) — — 602 600 MHz, 7.35-7.53 (m, 2H), 4.99-5.15 (m,2H), 4.30-4.46 DMSO- (m, 1H), 3.28 (br d, J = 3.43 Hz, 1H), 2.95-3.10(m, d6 3H), 2.86 (s, 3H), 2.79 (br dd, J = 8.25, 12.61 Hz, 1H),2.02-2.18 (m, 1H), 1.71-1.88 (m, 3H), 0.86- 1.01 (m, 4H) 603 500 MHz7.31-7.40 (m, 1H), 7.18-7.30 (m, 1H), 5.58 (q, B Chiralpak OJ, d₄-MeOH J= 7.18 Hz, 1H), 5.02-5.19 (m, 2H), 4.42-4.61 (m, 10% MeOH, 1H), 3.53(dtd, J = 1.56, 4.18, 12.39 Hz, 1H), 3.39 peak 2 (br d, J = 12.98 Hz,1H), 3.28 (s, 2H), 3.21-3.30 (m, 1H), 3.04-3.15 (m, 1H), 3.07 (br s,1H), 2.98 (dd, J = 8.82, 12.46 Hz, 1H), 2.17-2.29 (m, 1H), 1.89- 2..03(m, 1H), 1.56 (d, J = 7.01 Hz, 3H) 604 500 MHz mixture of rotamers: 8.68(d, J = 4.67 Hz, 1H), B Chiralpak AD, d₄-MeOH 8.53-8.62 (m, 1H), 7.90(dt, J = 1.82, 7.79 Hz, 1H), 20% MeOH, 7.83 (dt, J = 1.82, 7.79 Hz, 1H),7.54 (d, J = 7.79 Hz, peak 2 1H), 7.27-7.46 (m, 3H), 5.83 (q, J = 7.01Hz, 1H), 5.20-5.48 (m, 1H), 5.09 (d, J = 2.34 Hz, 1H), 4.37- 4.57 (m,1H), 3.48-3.57 (m, 1H), 3.34-3.46 (m, 1H), 3.05-3.21 (m, 2H), 3.03 (s,2H), 2.90-3.01 (m, 1H), 2.77 (s, 1H), 2.12-2.27 (m, 1H), 1.88- 2.01 (m,1H), 1.80 (d, J = 7.01 Hz, 1H), 1.64 (d, J = 7.01 Hz, 2H) 605 600 MHz,Mixture of rotamers: 7.41-7.52 (m, 1H), 7.29-7.40 — — DMSO- (m, 1H),4.94-5.01 (m, 2H), 4.26-4.49 (m, 1H), d6 3.42-3.50 (m, 1H), 3.07-3.11(m, 2H), 2.93-3.05 (m, 2H), 2.85 (s, 1H), 2.75-2.82 (m, 1H), 2.03- 2.15(m, 1H), 1.64-1.83 (m, 3H), 1.00-1.24 (m, 3H) 606 600 MHz, Mixture ofrotamers: 7.43-7.50 (m, 1H), 7.23-7.41 — — DMSO- (m, 1H), 4.98-5.05 (m,2H), 4.66-4.77 (m, 1H), d6 4.49-4.61 (m, 1H), 4.30-4.47 (m, 1H),3.75-3.86 (m, 1H), 3.60-3.69 (m, 1H), 3.18 (s, 2H), 2.94- 3.04 (m, 2H),2.93 (s, 1H), 2.77 (ddd, J = 8.56, 12.61, 18.68 Hz, 1H), 1.97-2.14 (m,1H), 1.71- 1.85 (m, 3H) 607 600 MHz, 7.34-7.50 (m, 2H), 4.91 (dd, J =14.95, 17.44 Hz, — — DMSO- 1H), 4.71-4.83 (m, 1H), 4.32-4.48 (m, 1H),3.76 d6 (dd, J = 8.25, 9.81 Hz, 1H), 3.56-3.70 (m, 2H), 3.20-3.30 (m,2H), 2.91-3.06 (m, 2H), 2.73-2.83 (m, 1H), 2.06-2.16 (m, 1H), 1.82-1.96(m, 1H), 1.73-1.82 (m, 1H), 1.69 (br dd, J = 3.74, 7.47 Hz, 1H), 1.57(td, J = 3.62, 7.40 Hz, 1H), 0.70-0.80 (m, 1H), 0.20 (d, J = 4.36 Hz,1H) 608 600 MHz, Mixture of diasteromers: 8.46-8.53 (m, 2H), 7.68- — —DMSO- 7.76 (m, 1H), 7.44-7.52 (m, 3H), 5.74-5.81 (m, d6 1H), 4.97-5.13(m, 2H), 4.32-4.48 (m, 1H), 2.94- 3.07 (m, 2H), 2.89 (d, J = 3.43 Hz,3H), 2.76-2.84 (m, 1H), 2.04-2.15 (m, 1H), 1.76-1.86 (m, 3H), 1.68 (brt, J = 6.85 Hz, 1H), 1.53 (dd, J = 2.49, 7.16 Hz, 3H) 609 600 MHz,Mixture of diasteromers: 7.43-7.53 (m, 1H), 7.38 — — DMSO- (qd, J =7.06, 10.59 Hz, 1H), 5.18 (dd, J = 7.63, d6 17.59 Hz, 1H), 4.88-5.03 (m,1H), 4.27-4.49 (m, 1H), 3.69-3.78 (m, 1H), 3.62 (dtd, J = 2.96, 5.98,8.76 Hz, 1H), 3.10-3.20 (m, 1H), 2.94-3.08 (m, 3H), 2.75-2.86 (m, 1H),2.08-2.20 (m, 2H), 1.90 (ddd, J = 3.43, 8.88, 12.61 Hz, 1H), 1.71-1.83(m, 4H), 0.81-0.90 (m, 1H) 610 500 MHz 7.35 (dd, J = 7.27, 10.64 Hz,1H), 7.28 (dd J = 7.14, B Chiralpak OJ, d₄-MeOH 10.25 Hz, 1H), 5.48-5.60(m, 1H), 5.01-5.19 (m, 10% MeOH, 2H), 4.51-4.66 (m, 1H), 3.56-3.64 (m,1H), 3.38- peak 1 3.45 (m, 2H), 3.28 (s, 3H), 3.03-3.13 (m, 1H),2.17-2.31 (m, 1H), 1.90-2.05 (m, 1H), 1.56 (d, J = 7.27 Hz, 3H) 611 600MHz, 7.25-7.58 (m, 2H), 4.90-5.18 (m, 3H), 4.28-4.49 — — DMSO- (m, 1H),3.93-4.00 (m, 1H), 3.54-3.79 (m, 3H), d6 2.89-3.08 (m, 4H), 2.71-2.84(m, 2H), 2.07-2.23 (m, 2H), 1.71-1.89 (m, 2H), 1.66-2.00 (m, 1H) 612 600MHz, Mixture of diasteroemers: 7.43-7.51 (m, 1H), 7.28- — — DMSO- 7.41(m, 1H), 4.93-5.20 (m, 2H), 4.74-4.85 (m, d6 1H), 4.30-4.55 (m, 1H),3.21-3.29 (m, 2H), 3.01- 3.05 (m, 3H), 2.96-3.00 (m, 1H), 2.75-2.90 (m,4H), 2.75-2.88 (m, 3H), 2.04-2.20 (m, 1H), 1.70- 1.87 (m, 3H), 1.14-1.35(m, 3H) 613 600 MHz, 8.53-8.60 (m, 2H), 7.43-7.51 (m, 2H), 7.31 (dd, — —DMSO- J = 5.45, 8.56 Hz, 2H), 5.69 (qum, J = 6.54 Hz, 1H), d6 4.99-5.18(m, 2H), 4.34-4.52 (m, 1H), 2.93-3.09 (m, 2H), 2.90 (d, J = 4.67 Hz,3H), 2.75-2.86 (m, 1H), 2.05-2.18 (m, 1H), 1.76-1.88 (m, 3H), 1.51 (dd,J = 2.96, 7.01 Hz, 3H) 614 600 MHz, Mixture of diasteromers: 7.45-7.53(m, 1H), 7.30- — — DMSO- 7.43 (m, 1H), 5.17-5.30 (m, 1H), 5.02-5.17 (m,d6 2H), 4.30-4.48 (m, 1H), 3.20-3.26 (m, 1H), 3.11 (s, 3H), 2.91-3.04(m, 2H), 2.73-2.82 (m, 1H), 2.03-2.15 (m, 1H), 1.80-1.86 (m, 1H),1.68-1.79 (m, 1H), 1.33-1.53 (m, 3H) 615 600 MHz, 7.40-7.55 (m, 2H),5.02-5.15 (m, 2H), 4.46 (s, — — DMSO- 2H), 4.31-4.44 (m, 1H), 3.27-3.30(m, 2H), 3.23 d6 (s, 3H), 2.97-3.06 (m, 1H), 2.93-3.05 (m, 1H), 2.78(dd, J = 8.10, 12.46 Hz, 1H), 2.06-2.18 (m, 1H), 1.71-1.82 (m, 1H) 616600 MHz, 7.41-7.52 (m, 1H), 7.29-7.40 (m, 1H), 4.94-5.01 — — DMSO- (m,2H), 4.26-4.49 (m, 1H), 3.42-3.50 (m, 1H), d6 3.07-3.11 (m, 2H),2.93-3.05 (m, 2H), 2.85 (s, 1H), 2.75-2.82 (m, 1H), 2.03-2.15 (m, 1H),1.64- 1.83 (m, 3H), 1.00-1.24 (m, 3H) 617 600 MHz, 7.45 (ddd, J = 7.47,10.98, 14.25 Hz, 2H), 5.00-5.14 — — DMSO- (m, 2H), 4.31-4.50 (m, 1H),3.49-3.54 (m, 2H), d6 3.38-3.48 (m, 4H), 3.19-3.24 (m, 1H), 2.93-3.06(m, 3H), 2.77 (dd, J = 8.41, 12.46 Hz, 1H), 2.03- 2.21 (m, 1H),1.73-1.88 (m, 1H), 0.88-1.03 (m, 4H) 618 600 MHz, 7.45-7.51 (m, 1H),7.33-7.44 (m, 1H), 4.82-5.09 — — DMSO- (m, 2H), 4.42-4.54 (m, 1H),4.26-4.39 (m, 1H), d6 3.91-4.21 (m, 2H), 3.71-3.86 (m, 2H), 3.43 (dt, J= 7.32, 10.98 Hz, 1H), 3.16-3.26 (m, 1H), 2.97- 3.07 (m, 2H), 2.75-2.86(m, 2H), 2.52-2.73 (m, 2H), 2.05-2.14 (m, 1H), 1.74-1.85 (m, 1H) 619 600MHz, 7.44-7.50 (m, 1H), 7.32-7.43 (m, 1H), 4.84-5.14 — — DMSO- (m, 2H),4.61-4.79 (m, 2H), 4.33-4.49 (m, 1H), d6 3.74-3.86 (m, 1H), 3.71 (s,1H), 3.60 (s, 1H), 3.25- 3.30 (m, 2H), 3.23 (br d, J = 11.52 Hz, 1H),2.91- 3.06 (m, 2H), 2.80 (dd, J = 8.25, 12.61 Hz, 1H), 2.07-2.18 (m,1H), 1.73-1.96 (m, 5H) 620 600 MHz, Mixture of isomers: 7.39-7.49 (m,2H), 4.91-5.08 — — DMSO- (m, 2H), 4.33-4.52 (m, 2H), 3.87-3.96 (m, 2H),d6 3.74-3.85 (m, 2H), 3.58-3.67 (m, 1H), 3.51 (t, J = 11.05 Hz, 1H),3.43 (dt, J = 3.11, 9.65 Hz, 1H), 3.21-3.27 (m, 2H), 2.94-3.05 (m, 2H),2.79 (td, J = 8.10, 12.46 Hz, 1H), 2.07-2.17 (m, 1H), 1.73- 1.85 (m,3H), 1.52-1.61 (m, 1H) 621 600 MHz, Mixture of diasteromers: 7.42-7.51(m, 1H), 7.38 — — DMSO- (dd, J = 7.47, 10.59 Hz, 1H), 4.93-5.13 (m, 2H),d6 4.29-4.47 (m, 1H), 3.65-3.88 (m, 1H), 3.40-3.57 (m, 1H), 3.19-3.23(m, 3H), 2.95-3.07 (m, 2H), 2.67-2.86 (m, 1H), 2.04-2.17 (m, 1H),1.71-1.85 (m, 3H) 622 600 MHz, 7.42-7.51 (m, 1H), 7.30-7.39 (m, 1H),4.91-5.10 — — DMSO- (m, 2H), 4.32-4.49 (m, 1H), 3.53-3.74 (m, 2H), d63.26 (br dd, J = 5.14, 7.32 Hz, 1H), 3.15 (s, 1H), 3.11-3.21 (m, 1H),2.93-3.05 (m, 2H), 2.78 (dd, J = 8.25, 12.61 Hz, 1H), 2.52-2.57 (m, 1H),2.04- 2.15 (m, 1H), 1.71-1.82 (m, 3H) 623 600 MHz, 7.43-7.52 (m, 1H),7.33 (dd, J = 7.16, 10.59 Hz, — — DMSO- 1H), 4.93-5.01 (m, 1H),4.81-4.90 (m, 1H), 4.31- d6 4.48 (m, 1H), 4.02-4.12 (m, 1H), 3.91-4.01(m, 1H), 3.80 (br d, J = 12.46 Hz, 1H), 3.58-3.70 (m, 1H), 3.17-3.26 (m,1H), 2.91-3.03 (m, 2H), 2.72- 2.85 (m, 2H), 2.56-2.65 (m, 1H), 2.02-2.20(m, 1H), 1.68-1.81 (m, 2H) 624 600 MHz, 8.32-8.47 (m, 2H), 7.35-7.53 (m,2H), 6.61-6.74 — — DMSO- (m, 1H), 5.03-5.16 (m, 2H), 4.32-4.48 (m, 1H),d6 3.83-3.93 (m, 2H), 3.77 (br t, J = 4.20 Hz, 2H), 3.67-3.73 (m, 4H),3.60-3.64 (m, 2H), 2.95-3.06 (m, 2H), 2.81 (dd, J = 7.94, 12.61 Hz, 1H),2.05- 2.19 (m, 1H), 1.75-1.86 (m, 1H) 625 600 MHz, Mixture of Rotamers:7.44-7.53 (m, 1H), 7.36 (dd, — — DMSO- J = 7.32, 10.74 Hz, 1H),4.66-4.90 (m, 2H), 4.50- d6 4.65 (m, 1H), 4.31-4.48 (m, 1H), 4.10-4.28(m, 2H), 3.99-4.09 (m, 1H), 2.91-3.09 (m, 2H), 2.79 (dt, J = 8.56, 13.16Hz, 1H), 2.20-2.32 (m, 1H), 2.08-2.16 (m, 2H), 2.00 (td, J = 5.61, 15.26Hz, 1H), 1.69-1.89 (m, 3H), 0.77-0.92 (m, 6H) 626 600 MHz, Mixture ofRotamers: 7.47 (dd, J = 7.47, 11.21 — — DMSO- Hz, 1H), 7.39 (dd, J =7.16, 10.59 Hz, 1H), 6.61- d6 6.99 (m, 1H), 4.79-5.01 (m, 3H), 4.30-4.48(m, 1H), 3.63-3.94 (m, 3H), 3.51-3.61 (m, 2H), 2.96- 3.07 (m, 2H), 2.79(ddd, J = 1.25, 8.33, 12.53 Hz, 1H), 2.17-2.31 (m, 1H), 1.98-2.15 (m,3H), 1.73- 1.81 (m, 1H) 627 600 MHz, Mixture of diastereomers: 7.43-7.53(m, 1H), 7.28- — — DMSO- 7.40 (m, 1H), 4.98-5.28 (m, 3H), 4.30-4.51 (m,d6 1H), 4.01-4.26 (m, 1H), 3.74-3.98 (m, 4H), 3.44- 3.53 (m, 1H),3.40-3.59 (m, 1H), 2.94-3.10 (m, 3H), 2.72-2.87 (m, 1H), 2.06-2.19 (m,1H), 1.71- 1.94 (m, 1H) 628 600 MHz, Mixture of diastereomers: 7.23-7.49(m, 2H), 4.91- — — DMSO- 5.18 (m, 4H), 4.29-4.49 (m, 1H), 3.49-4.15 (m,d6 4H), 2.92-3.09 (m, 3H), 2.71-2.82 (m, 1H), 2.04- 2.16 (m, 1H),1.29-1.90 (m, 8H) 629 600 MHz, 7.44-7.52 (m, 1H), 7.41 (dd, J = 7.32,10.74 Hz, — — DMSO- 1H), 4.94-5.14 (m, 2H), 4.34-4.49 (m, 1H), 4.23- d64.32 (m, 1H), 3.97-4.06 (m, 1H), 3.21 (br d, J = 1.25 Hz, 1H), 2.95-3.05(m, 2H), 2.74-2.91 (m, 2H), 2.06-2.16 (m, 1H), 2.01 (td, J = 2.76, 5.99Hz, 1H), 1.88-1.96 (m, 2H), 1.72-1.85 (m, 2H), 1.60- 1.72 (m, 1H),1.43-1.53 (m, 1H), 1.40 (s, 3H) 630 600 MHz, 8.35-8.57 (m, 1H),7.59-7.69 (m, 1H), 7.26-7.53 — — DMSO- (m, 2H), 7.24 (dd, J = 4.83, 7.63Hz, 1H), 5.02-5.21 d6 (m, 2H), 4.66-4.93 (m, 1H), 4.60-4.95 (m, 1H),4.25-4.48 (m, 1H), 3.92 (br t, J = 5.92 Hz, 1H), 3.80-3.87 (m, 1H),2.71-3.14 (m, 5H), 1.97-2.15 (m, 1H), 1.62-1.80 (m, 1H) 631 600 MHz,7.19-7.28 (m, 2H), 6.88-6.96 (m, 1H), 6.00-6.28 — — DMSO- (m, 1H),5.11-5.23 (m, 2H), 4.31-4.50 (m, 1H), d6 3.76 (dt, J = 3.74, 15.26 Hz,2H), 2.92-3.08 (m, 3H), 2.81 (dd, J = 8.25, 12.61 Hz, 1H), 2.07-2.18 (m,1H), 1.70-1.84 (m, 1H), 0.89-1.07 (m, 4H) 632 600 MHz, 8.49-8.55 (m,1H), 7.81-7.90 (m, 1H), 7.42-7.51 — — DMSO- (m, 2H), 7.33-7.40 (m, 1H),5.00-5.17 (m, 4H), d6 4.67-4.79 (m, 2H), 4.32-4.47 (m, 1H), 3.36-3.42(m, 1H), 2.95-3.09 (m, 2H), 2.82 (dd, J = 7.94, 12.61 Hz, 1H), 2.05-2.16(m, 1H), 1.76-1.87 (m, 2H) 633 600 MHz, Mixture of diasteromers:7.43-7.52 (m, 1H), 7.29- — — DMSO- 7.41 (m, 1H), 4.91-5.05 (m, 2H),4.29-4.50 (m, d6 1H), 3.55-3.89 (m, 3H), 3.36-3.49 (m, 2H), 3.19- 3.28(m, 1H), 3.14 (s, 2H), 2.94-3.05 (m, 2H), 2.87 (s, 1H), 2.73-2.83 (m,1H), 2.51-2.66 (m, 1H), 2.02-2.15 (m, 1H), 1.86-1.94 (m, 1H), 1.72-1.84(m, 2H), 1.43-1.64 (m, 1H) 634 600 MHz, 7.22-7.29 (m, 1H), 7.06-7.21 (m,1H), 6.87-6.96 — — DMSO- (m, 1H), 6.01-6.52 (m, 1H), 4.97-5.13 (m, 2H),d6 4.29-4.50 (m, 1H), 3.68-4.05 (m, 2H), 3.57 (q, J = 7.16 Hz, 1H), 3.40(br d, J = 7.16 Hz, 1H), 2.93- 3.06 (m, 2H), 2.71-2.89 (m, 1H),2.06-2.15 (m, 1H), 1.78 (ddd, J = 3.58, 6.46, 9.58 Hz, 1H), 1.24 (t, J =7.16 Hz, 2H), 1.06 (t, J = 7.01 Hz, 1H) 635 600 MHz, 7.21-7.27 (m, 1H),7.16 (dd, J = 4.67, 8.72 Hz, 1H), — — DMSO- 7.08 (dd, J = 4.67, 8.72 Hz,1H), 6.88-6.98 (m, 1H), d6 4.98-5.20 (m, 2H), 4.15-4.52 (m, 1H), 4.21(q, J = 9.65 Hz, 1H), 3.63 (q, J = 7.06 Hz, 2H), 3.42 (brd, J = 6.85 Hz,1H), 2.89-3.07 (m, 2H), 2.69-2.85 (m, 1H), 2.03-2.13 (m, 1H), 1.69-1.81(m, 1H), 1.28 (t, J = 7.16 Hz, 2H), 1.07 (t, J = 7.01 Hz, 1H) 636 600MHz, 7.39-7.56 (m, 2H), 4.92 (br d, J = 3.43 Hz, 3H), — — DMSO- 4.81(dd, J = 3.43, 7.47 Hz, 1H), 4.34-4.49 (m, 1H), d6 3.81 (ddd, J = 3.89,7.71, 9.58 Hz, 1H), 3.56-3.71 (m, 1H), 2.98-3.09 (m, 3H), 2.80 (dd, J =8.10, 12.77 Hz, 1H), 2.05-2.30 (m, 8H) 637 600 MHz, 7.43-7.50 (m, 1H),7.37 (dd, J = 7.16, 10.59 Hz, — — DMSO- 1H), 4.99-5.11 (m, 1H),4.88-4.99 (m, 1H), 4.53- d6 4.62 (m, 1H), 4.30-4.48 (m, 1H), 4.15 (tt, J= 3.89, 11.99 Hz, 1H), 2.98-3.05 (m, 1H), 2.91-2.98 (m, 3H), 2.78 (td, J= 7.43, 12.53 Hz, 1H), 2.72 (s, 1H), 2.07-2.14 (m, 1H), 1.86 (br d, J =11.21 Hz, 3H), 1.73-1.80 (m, 1H), 1.66 (br d, J = 8.41 Hz, 2H),1.52-1.60 (m, 1H), 1.48 (br dd, J = 3.11, 9.34 Hz, 1H), 1.29-1.37 (m,1H), 1.13-1.26 (m, 2H) 638 600 MHz, Mixture of rotamers: 8.68 (dd, J =0.78, 4.67 Hz, B Chiralpak DMSO- 1H), 8.58 (dd, J = 0.78, 4.93 Hz, 1H),7.79-7.95 (m, AD, 20% d6 1H), 7.54 (d, J = 7.79 Hz, 1H), 7.26-7.46 (m,3H), MeOH, peak 5.83 (q, J = 7.18 Hz, 1H), 5.41 (d, J = 6.75 Hz, 1H), 15.22-5.37 (m, 1H), 5.04-5.14 (m, 1H), 4.35-4.61 (m, 1.H), 3.50-3.61 (m,1H), 3.35-3.47 (m, 1H), 3.05-3.20 (m, 2H), 3.02 (s, 1H), 2.89-2.98 (m,1H), 2.76 (s, 1H), 2.12-2.28 (m, 1H), 1.86-2.01 (m, 1H), 1.80 (d, J =6.75 Hz, 1H), 1.63 (d, J = 7.27 Hz, 1H) 639 600 MHz, 7.42-7.52 (m, 1H),7.32-7.41 (m, 1H), 5.04-5.26 — — DMSO- (m, 1H), 4.83-5.02 (m, 1H),4.55-4.65 (m, 1H), d6 4.31-4.48 (m, 1H), 4.10-4.26 (m, 1H), 3.85-3.95(m, 1H), 3.77 (br d, J = 11.21 Hz, 1H), 3.58-3.68 (m, 1H), 3.46-3.56 (m,1H), 3.13-3.21 (m, 1H), 2.92-3.07 (m, 2H), 2.76-2.87 (m, 1H), 2.59-2.71(m, 1H), 2.02-2.26 (m, 2H), 1.86-1.93 (m, 1H), 1.66-1.82 (m, 3H),1.50-1.60 (m, 2H), 1.21-1.35 (m, 1H) 640 600 MHz, 7.46 (dd, J = 7.47,10.90 Hz, 1H), 7.37 (dd, J = 7.47, — — DMSO- 10.90 Hz, 1H), 4.91-5.08(m, 3H), 4.30-4.49 (m, d6 1H), 3.69-3.94 (m, 4H), 3.05-3.15 (m, 1H),2.93- 3.05 (m, 3H), 2.79 (dd, J = 8.25, 12.61 Hz, 1H), 2.04-2.17 (m,2H),1.67-1.86 (m, 4H), 1.41-1.50 (m, 1H), 1.24-1.33 (m, 1H) 641 600 MHz,8.66-8.70 (m, 1H), 8.13 (s, 1H), 7.42-7.51 (m, — — DMSO- 2H), 5.44-5.53(m, 1H), 4.81-4.90 (m, 2H), 4.77 d6 (q, J = 9.03 Hz, 1H), 4.55 (dt, J =5.29, 8.88 Hz, 1H), 4.33-4.49 (m, 2H), 4.24 (dd, J = 5.29, 10.28 Hz,1H), 3.15-3.28 (m, 1H), 3.01-3.08 (m, 2H), 2.82 (dd, J = 8.41, 12.46 Hz,1H), 2.10-2.17 (m, 1H), 1.90-2.07 (m, 1H), 1.79-1.87 (m, 1H) 642 600MHz, 7.45-7.50 (m, 1H), 7.41 (br t, J = 8.25 Hz, 1H), — — DMSO-6.50-6.64 (m, 1H), 5.07-5.19 (m, 1H), 4.94-5.03 d6 (m, 1H), 4.21-4.50(m, 2H), 3.91-4.05 (m, 1H), 3.73-3.85 (m, 1H), 3.53-3.69 (m, 2H),2.91-3.10 (m, 5H), 2.71-2.86 (m, 2H), 2.56-2.65 (m, 1H), 2.11-2.18 (m,1H), 1.74-1.82 (m, 1H) 643 600 MHz, 7.48 (dd, J = 7.47, 11.21 Hz, 1H),7.35 (ddd, — — DMSO- J = 5.61, 7.08, 10.67 Hz, 1H), 4.92-5.18 (m, 2H),d6 4.30-4.47 (m, 1H), 3.74-3.92 (m, 2H), 3.57-3.73 (m, 3H), 3.47-3.53(m, 1H), 3.32-3.44 (m, 6H), 3.22-3.27 (m, 1H), 2.93-3.05 (m, 3H),2.74-2.80 (m, 2H), 2.01-2.16 (m, 2H), 1.73-1.91 (m, 3H), 1.47-1.67 (m,1H) 644 600 MHz, 7.81-8.03 (m, 1H), 7.44-7.50 (m, 1H), 7.40 (dd, — —DMSO- J = 7.47, 10.59 Hz, 1H), 4.92-5.22 (m, 2H), 4.10- d6 4.47 (m, 2H),3.77-4.02 (m, 3H), 3.47-3.60 (m, 1H), 3.44-3.71 (m, 1H), 3.13-3.25 (m,2H), 2.99- 3.09 (m, 2H), 2.73-2.86 (m, 2H), 2.59-2.69 (m, 3H), 2.05-2.19(m, 1H), 1.70-1.85 (m, 1H) 645 600 MHz, 7.42-7.52 (m, 1H), 7.31-7.42 (m,1H), 4.72-5.01 — — DMSO- (m, 2H), 4.32-4.53 (m, 1H), 3.89-4.17 (m, 1H),d6 3.71-3.85 (m, 1H), 3.53-3.67 (m, 1H), 3.43 (br dd, J = 5.92, 14.01Hz, 1H), 3.36-3.40 (m, 2H), 3.17 (d, J = 4.98 Hz, 1H), 3.11-3.22 (m,1H), 2.97-3.08 (m, 5H), 2.75-2.83 (m, 1H), 2.59-2.71 (m, 1H), 2.09- 2.31(m, 2H), 1.74-1.88 (m, 2H) 646 600 MHz, 7.96-8.09 (m, 1H), 7.41-7.53 (m,2H), 5.08-5.27 — — DMSO- (m, 2H), 5.03 (s, 1H), 4.75-4.86 (m, 1H), 4.33-d6 4.49 (m, 2H), 4.13-4.22 (m, 2H), 3.96-4.07 (m, 1H), 3.24-3.28 (m,1H), 2.94-3.05 (m, 2H), 2.75- 2.83 (m, 1H), 2.01-2.15 (m, 1H), 1.72-1.84(m, 2H) 647 600 MHz, Mixture of Diasteromers: 7.44-7.50 (m, IB), 7.37- —— DMSO- 7.43 (m, 1H), 5.13 (dt J = 6.23, 18.22 Hz, 1H), 4.94 d6 (br dd,J = 13.86, 17.28 Hz, 1H), 4.31-4.50 (m, 1H), 4.06-4.21 (m, 1H),3.80-3.94 (m, 2H), 3.48-3.69 (m, 2H), 3.39-3.46 (m, 3H), 3.25 (s, 3H),3.07- 3.11 (m, 1H), 2.94-3.03 (m, 2H), 2.74-2.86 (m, 2H), 2.58-2.64 (m,1H), 2.06-2.15 (m, IB), 1.71- 1.87 (m, 1H) 648 600 MHz, 7.46 (dd, J =7.47, 10.90 Hz, 1H), 7.36 (dd, J = 7.32, — — DMSO- 10.74 Hz, 1H),4.76-5.01 (m, 3H), 4.29-4.47 (m, d6 1H), 3.67-3.77 (m, 1H), 3.42-3.55(m, 2H), 2.95- 3.18 (m, 3H), 2.74-2.84 (m, 1H), 2.04-2.15 (m, 1H),1.73-1.98 (m, 4H), 1.28-1.37 (m, 3H) 649 600 MHz, 7.44-7.51 (m, 1H),7.32-7.41 (m, 1H), 4.99-5.14 — — DMSO- (m, 2H), 4.29-4.48 (m, 1H),3.54-3.75 (m, 5H), d6 3.18-3.26 (m, 3H), 3.11-3.17 (m, 2H), 2.97-3.06(m, 2H), 2.94 (s, 3H), 2.74-2.83 (m, 1H), 2.08- 2.19 (m, 1H), 1.75-1.95(m, 3H) 650 600 MHz, Mixture of Diasteromers: 7.31-7.53, (m, 2H), 4.93-— — DMSO- 5.22 (m, 2H), 4.49-4.64 (m, 1H), 4.31-4.46 (m, d6 1H),3.73-3.82 (m, 3H), 3.44-3.69 (m, 5H), 2.94- 3.06 (m, 3H), 2.72-2.85 (m,1H), 2.05-2.30 (m, 4H), 1.97 (d, 3=12.46 Hz, 3H), 1.86-1.92 (m, 2H),3.25 (q, J = 7.16 Hz, 2H), 3.03 (q, J = 6.75 Hz, 2H) 65` 600 MHz,7.43-7.51 (m, 1H), 7.35-7.43 (m, 1H), 5.04-5.19 — — DMSO- (m, 1H),4.90-5.03 (m, 1H), 4.57 (tt, J = 3.35, 12.22 d6 Hz, 1H), 4.33-4.48 (m,1H), 3.35-3.45 (m, 3H), 3.17-3.28 (m, 3H), 3.06 (br d, J = 11.52 Hz,1H), 3.00 (s, 3H), 2.73-2.83 (m, 2H), 2.06-2.31 (m, 4H), 1.88 (br d, J =10.90 Hz, 2H), 1.71-1.83 (m, 1H) 652 600 MHz, Mixture of Diasteromers:7.34-7.49 (m, 2H), 4.93- — — DMSO- 5.05 (m, 2H), 4.33-4.50 (m, 1H),3.40-3.60 (m, d6 3H), 3.20-3.26 (m, 3H), 3.3.4-3.18 (m, 3H), 2.95- 3.10(m, 3H), 2.78 (ddd, J = 7.32, 8.95, 12.69 Hz, 3H), 2.05-2.24 (m, 2H),1.65-1.91 (m, 2H) 653 600 MHz, 7.43-7.50 (m, 1H), 7.31-7.39 (m, 1H),5.04-5.16 — — DMSO- (m, 1H), 4.93-5.03 (m, 1H), 4.31-4.50 (m, 2H), d64.02-4.12 (m, 1H), 3.18-3.29 (m, 2H), 3.09 (br t, J = 12.77 Hz, 1H),2.91-3.04 (m, 2H), 2.80 (td, J = 7.63, 12.77 Hz, 1H), 2.55-2.64 (m, 1H),2.06- 2.19 (m, 1H), 1.88 (br s, 1H), 1.75-1.84 (m, 3H), 1.62-1.72 (m,1H), 1.31 (br d, J = 4.67 Hz, 6H), 1.07-1.15 (m, 1H) 654 600 MHz,7.80-7.93 (m, 1H), 7.42-7.50 (m, 1H), 7.32-7.39 — — DMSO- (m, 1H),4.89-5.17 (m, 2H), 4.31-4.48 (m, 1H), d6 3.74-3.93 (m, 2H), 3.40 (br dd,J = 9.34, 13.70 Hz, 1H), 3.11-3.19 (m, 1H), 2.94-3.04 (m, 3H), 2.72-2.87 (m, 2H), 2.53-2.65 (m, 3H), 2.05-2.24 (m, 2H), 1.77-1.90 (m, 4H),1.59-1.74 (m, 2H) 655 600 MHz, Mixture of Rotamers: 8.43-8.56 (m, 2H),7.69 (td, — — DMSO- J = 1.87, 7.79 Hz, 1H), 7.47 (dd, J = 7.32, 11.05Hz, d6 1H), 7.33-7.39 (m, 1H), 7.25-7.31 (m, 1H), 5.25 (s, 2H), 4.62 (s,2H), 4.32-4.50 (m, 1H), 3.64-3.72 (m, 2H), 3.53 (br t, J = 4.98 Hz, 2H),3.36-3.42 (m, 2H), 2.93-3.06 (m, 2H), 2.71-2.82 (m, 1H), 2.01- 2.13 (m,1H) 1.72-1.89 (m, 1H) 656 600 MHz, Mixture of Rotamers: 7.47 (dd, J =7.63, 11.06 Hz, — — DMSO- 1H), 7.33-7.42 (m, 1H), 5.04-5.21 (m, 2H),4.31- d6 4.48 (m, 1H), 3.86-4.07 (m, 3H), 3.51 (t, J = 6.85 Hz, 1H),3.41-3.46 (m, 1H), 3.41 (br s, 1H), 3.20- 3.28 (m, 1H), 2.94-3.07 (m,2H), 2.77-2.84 (m, 1H), 2.72 (t, J = 6.85 Hz, 1H), 2.04-2.17 (m, 1H),1.69-1.87 (m, 5H) 657 600 MHz, Mixture of Roatmers: 7.36-7.50 (m, 2H),4.92-5.14 — — DMSO- (m, 2H), 4.30-4.50 (m, 1H), 4.03-4.24 (m, 1H), d63.76-3.96 (m, 1H), 3.12-3.24 (m, 1H), 2,98-3.08 (m, 4H), 2.77-2.89 (m,5H), 2.61-2.73 (m, 1H), 2.09-2.21 (m, 1H), 1.76-1.94 (m, 4H), 1.48-1.67(m, 2H) 658 600 MHz, 7.44-7.50 (m, 1H), 7.34-7.42 (m, 1H), 4.95-5.13 — —DMSO- (m, 2H), 4.29-4.47 (m, 2H), 4.00-4.11 (m, 1H), d6 3.48 (d, J =1.56 Hz, 2H), 3.36 (s, 3H), 3.22-3.28 (m, 2H), 2.93-3.07 (m, 2H),2.54-2.87 (m, 2H), 2.08-2.19 (m, 1H), 1.98-2.05 (m, 1H), 1.94 (br d, J =13.39 Hz, 1H), 1.76-1.88 (m, 3H), 1.63-1.73 (m, 1H), 1.44-1.53 (m, 1H)659 600 MHz, 7.37-7.51 (m, 2H), 4.93-5.21 (m, 2H), 4.32-4.51 — — DMSO-(m, 3H), 3.95-4.07 (m, 2H), 3.59-3.69 (m, 1H), d6 3.09-3.22 (m, 2H),2.93-3.07 (m, 3H), 2.61-2.83 (m, 2H), 2.04-2.23 (m, 1H), 1.74-1.96 (m,3H) 660 600 MHz, 7.51 (d, 3=3.58 Hz, 1H), 7.24-7.29 (m, 3H), 6.91- ISFC: DMSO- 6.97 (m, 1H), 5.07 (s, 2H), 4.31-4.46 (m, 1H), Chiralpak d63.31-3.43 (m, 2H), 2.95-3.10 (m, 2H), 2.78-2.87 AY-H, 10% (m, 1H),2.07-2.16 (m, 1H), 1.73-1.84 (m, 1H) IPA Peak 1 661 600 MHz, 9.04-9.14(m, 1H), 7.21-7.27 (m, 1H), 7.13-7.20 I SFC: DMSO- (m, 1H), 6.89-6.97(m, 1H), 4.80 (s, 2H), 4.30- Chiralpak d₆ 4.51 (m, 1H), 3.93-4.06 (m,2H), 3.37-3.47 (m, AY-H, 10% 2H), 2.97-3.08 (m, 2H), 2.77-2.87 (m, 1H),2.04- IPA Peak 1 2.16 (m, 1H), 1.72-1.88 (m, 1H) 662 600 MHz, 7.18-7.27(m, 2H), 6.93 (ddd, J = 9.85, 8.76, 2.49 I SFC: DMSO- Hz, 1H), 5.17-5.28(m, 2H), 4.32-4.50 (m, 1H), Chiralpak d₆ 4.13-4.25 (m, 2H), 2.95-3.10(m, 3H), 2.62-2.91 AY-H, 10% (m, 2H), 2.52-2.57 (m, 1H), 2.07-2.18 (m,1H), IPA Peak 1 1.71-1.83 (m, 1H), 0.98-1.13 (m, 4H) 663 600 MHz,7.15-7.25 (m, 1H), 7.06 (dd, J = 8.68, 4.87 Hz, 1H), I SFC: DMSO- 6.91(t, J = 9.22 Hz, 1H), 4.95-5.03 (m, 2H), 4.38- Chiralpak d₆ 4.49 (m,1H), 3.60-3.67 (m, 1H), 3.54-3.60 (m, AY-H, 10% 1H), 3.47-3.53 (m, 1H),3.39-3.47 (m, 2H), 3.34- IPA Peak 1 3.39 (m, 3H), 3.21-3.27 (m, 3H),2.96-3.09 (m, 2H), 2.81 (dt J = 12.53, 9.26 Hz, 2H), 2.06-2.15 (m, 1H),1.74-1.83 (m, 1H) 664 500 MHz, 7.13-7.24 (m, 2H), 6.87-7.00 (m, 1H),4.96-5.14 F Chiralpak IF, METHA (m, 2H), 4.34-4.55 (m, 1H), 4.04-4.17(m, 1H), 30% MeOH NOL-d₄ 3.64-3.97 (m, 3H), 3.47-3.57 (m, 1H), 3.38-3.46w/ 0.2% (m, 1H), 3.30-3.34 (m, 2H), 3.06-3.21 (m, 4H), DEA, peak 2 2.93(m, 1H), 2.16-2.44 (m, 2H), 1.87-2.10 (m, 2H) 665 500 MHz, 7.13-7.23 (m,2H), 6.89-6.99 (m, 1H), 5.03 (s, F Chiralpak IF, METHA 2H), 4.35-4.54(m, 1H), 4.05-4.16 (m, 1H), 3.65- 30% MeOH NOL-d₄ 3.98 (m, 3H),3.48-3.58 (m, 1H), 3.35-3.49 (m, w/ 0.2% 1H), 3.32 (td, J = 1.57, 3.21Hz, 3H), 3.06-3.14 (m, DEA, peak 1 2H), 2.89-3.02 (m, 2H), 2.15-2.45 (m,2H), 1.85- 2.09 (m, 2H) 666 600 MHz, 8.90-9.00 (m, 1H), 8.49-8.58 (m,1H), 7.73-7.81 B Chiralpak IC DMSO- (m, 1H), 7.36-7.42 (m, 1H),7.26-7.31 (m, 1H), 30% MeOH, d₆ 7.16-7.24 (m, 2H), 6.86-6.97 (m, 1H),4.95-5.09 peak 2 (m, 1H), 4.70-4.84 (m, 2H)5 4.27-4.47 (m, 1H),3.38-3.48 (m, 1H), 3.33-3.38 (m, 1H), 2.94-3.07 (m, 2H), 2.76-2.84 (m,1H), 2.03-2.16 (m, 1H), 1.74-1.81 (m, 1H), 1.38-1.49 (m, 3H) 667 500MHz, 7.07-7.25 (m, 2H), 6.90-7.01 (m, 1H), 5.16-5.32 F Chiralpak IF,METHA (m, 1H), 5.01-5.16 (m, 1H), 4.32-4.55 (m, 2H), AD-H, 15% NOL-d₄4.06-4.32 (m, 2H), 3.67-4.04 (m, 4H), 3.45-3.55 MeOH with (m, 1H),3.36-3.45 (m, 1H), 3.04-3.19 (m, 2H), 0.2% DEA, 2.88-3.02 (m, 1H),2.00-2.61 (m, 3H), 1.81-1.98 peak 2 (m, 1H) 668 600 MHz, 8.63-8.71 (m,1H), 7.20-7.25 (m, 1H), 7.13-7.20 I SFC: DMSO- (m, 1H), 6.87-6.98 (m,1H), 4.63 (s, 2H), 4.31- Chiralpak d₆ 4.48 (m, 1H), 4.16-4.28 (m, 1H),3.35-3.47 (m, AY-H, 10% 1H), 2.95-3.10 (m, 2H), 2.76-2.88 (m, 1H), 2.15-IPA Peak 1 2.24 (m, 2H), 2.05-2.14 (m, 1H), 1.86-1.99 (m, 3H), 1.76-1.86(m, 1H), 1.57-1.71 (m, 2H) 669 600 MHz, 8.61-8.72 (m, 1H), 7.15-7.29 (m,2H), 6.85-6.97 I SFC: DMSO- (m, 1H), 4.69 (d, J = 9.19 Hz, 2H),4.31-4.50 (m, Chiralpak d₆ 1H), 4.04-4.15 (m, 1H), 3.36-3.49 (m, 2H),2.96- AY-H, 10% 3.13 (m, 2H), 2.73-2.88 (m, 2H), 2,63-2.73 (m, IPA Peak1 1H), 2.07-2.19 (m, 1H), 1.76-1.86 (m, 1H), 1.21 (d, J = 6.77 Hz, 3H)670 600 MHz, 8.63-8.74 (m, 1H), 7.16-7.29 (m, 2H), 6.85-6.96 I SFC:DMSO- (m, 1H), 4.61-4.77 (m, 2H), 4.30-4.50 (m, 1H), Chiralpak d₆4.04-4.15 (m, 1H), 3.35-3.47 (m, 2H), 2.98-3.11 AY-H, 10% (m, 2H),2.81-2.87 (m, 1H), 2.75-2.80 (m, 1H), IPA Peak 1 2.66-2.71 (m, 1H),2.08-2.20 (m, 1H), 1.75-1.88 (m, 1H), 1.21 (d, J = 6.77 Hz, 3H) 671 600MHz, 7.23-7.34 (m, 1H), 7.12-7.14 (m, 1H), 6.98 (t, I SFC: DMSO- J =9.31 Hz, 1H), 4.95-5.09 (m, 2H), 4.77-4.86 (m, Chiralpak d₆ 1 H),3.66-3.76 (m, 1H), 3.57-3.62 (m, 1H), 3.46- AY-H, 10% 3.56 (m, 4H), 3.37(s, 3H), 3.31-3.35 (m, 2H), IPA Peak 1 3.07-3.12 (m, 2H), 2.91-3.05 (m,1H), 2.16-2.23 (m, 1H), 1.76-1.88 (m, 1 H), 1.04 (t, J = 7.01 Hz, 3H)672 500 MHz, 7.08-7.23 (m, 2H), 6.89-7.00 (m, 1H), 5.15-5.32 F SFC:METHA (m, 1H), 5.02-5.14 (m, 1H), 4.30-4.55 (m, 2H), Chiralpak NOL-d₄4.07-4.28 (m, 2H), 3.69-4.05 (m, 4H), 3.47-3.57 AY-H, 10% (m, 1H),3.35-3.44 (m, 1H), 3.03-3.19 (m, 2H), IPA Peak 1 2.88-2.99 (m, 1H),1.99-2.61 (m, 3H), 1.82-1.99 (m, 1H) 673 600 MHz, 8.55-8.63 (m, 1H),7.20-7.27 (m, 1H), 7.13-7.19 I SFC: DMSO- (m, 1H), 6.88-6.99 (m, 1H),4.63-4.71 (m, 2H), Chiralpak d₆ 4.31-4.49 (m, 1H), 3.35-3.47 (m, 4H),2.96-3.11 AY-H, 10% (m, 2H), 2.79-2.87 (m, 1H), 2.41-2.48 (m, 2H), IPAPeak 1 2.07-2.15 (m, 1H), 1.74-1.86 (m, 1H) 674 600 MHz, 8.86-9.01 (m,1H), 8.49-8.62 (m, 1H), 7.71-7.82 I SFC: DMSO- (m, 1H), 7.34-7.43 (m,1H), 7.26-7.32 (m, 1H), Chiralpak d₆ 7.14-7.24 (m, 2H), 6.86-6.96 (m,1H), 4.97-5.07 AY-H, 10% (m, 1H), 4.68-4.86 (m, 2H), 4.30-4.48 (m, 1H),IPA Peak 1 3.35-3.47 (m, 2H), 2.95-3.08 (m, 2H), 2.76-2.86 (m, 1H),2.03-2.15 (m, 1H), 1.72-1.83 (m, 1H), 1.43 (d, J = 7.01 Hz, 3H) 675 600MHz, 8.62-8.77 (m, 1H), 7.14-7.26 (m, 2H), 6.83-6.98 B Chiralpak DMSO-(m, 1H), 4.67 (d, J = 5.29 Hz, 2H), 4.33-4.48 (m, AZ-H, 35% d₆ 1H),4.26-4.32 (m, 1H), 3.79-3.86 (m, 1H), 3.73- MeOH, peak 1 3.78 (m, 1H),3.67-3.73 (m, 1H) 3.50-3.56 (m, 1H), 3.37-3.46 (m, 2H), 2.97-3.09 (m,2H), 2.76- 2.85 (m, 1H), 2.07-2.17 (m, 2H), 1.74-1.85 (m, 2H) 676 600MHz, 8.65-8.73 (m, 1H), 7.16-7.27 (m, 2H), 6.89-6.97 B Chiralpak DMSO-(m, 1H), 4.67 (s, 2H), 4.33-4.47 (m, 1H), 4.25- AZ-H, 35% d₆ 4.32 (m,1H), 3.80-3.88 (m, 1H), 3.73-3.79 (m, MeOH, peak 2 1H), 3.66-3.73 (m,1H), 3.49-3.57 (m, 1H), 3.37- 3.46 (m, 2H), 2.96-3.10 (m, 2H), 2.77-2.87(m, 1H), 2.07-2,18 (m, 2H), 1.74-1.86 (m, 2H) 677 600 MHz 8.18 (s, 2H),7.17-7.25 (m, 2H), 6.93 (t, J = 9.30 I SFC: DMSO- Hz, 1H), 4.59-4.76 (m,2H), 4.44-4.53 (m, 1H), Chiralpak d₆ 4.34-4.43 (m, 1H), 4.07-4.22 (m,1H), 3.84 (br t, AY-H, 10% J = 7.75 Hz, 1H), 3.28-3.47 (m, 2H),3.01-3.21 (m, IPA Peak 1 4H), 2.79-2.95 (m, 1H), 2.52-2.57 (m, 1H),2.40- 2.48 (m, 1H), 2.09-2.17 (m, 1H), 1.77-1.90 (m, 2H), 1.53 (d, J =6.23 Hz, 1H), 1.35 (dd, J = 1.40, 6.31 Hz, 1H) 678 600 MHz 7.16-7.25 (m,2H), 6.91 (t, J = 9.20 Hz, 1H), 5.08- I SFC: DMSO- 5.23 (m, 1H),4.81-4.95 (m, 1H), 4.45 (dt, J = 4.17, Chiralpak d₆ 7.88 Hz, 1H),4.30-4.39 (m, 1H), 4.13 (br s, 1H), AY-H, 10% 4.00 (br d, J = 13.47 Hz,1H), 3.82-3.93 (m, 1H), IPA Peak 1 3.60-3.73 (m, 2H), 3.41-3.53 (m, 2H),2.96-3.07 (m, 2H), 2.77-2.86 (m, 1H), 2.12 (br s, 2H), 1.75- 1.84 (m,1H), 1.37 (br d, J = 5.61 Hz, 1H), 1.14- 1.20 (m, 2H) 679 600 MHz7.15-7.25 (m, 2H), 6.91 (t, J = 9.32 Hz, 1H), 4.87 I SFC: DMSO- (s, 1H),4.29-4.39 (m, 1H), 4.05 (dt, J = 2.61, 6.60 Chiralpak d₆ Hz, 1H),3.61-3.75 (m, 1H), 3.42-3.59 (m, 3H), AY-H, 10% 2.95-3.12 (m, 2H),2.77-2.85 (m, 1H), 2.52-2.55 IPA Peak 1 (m, 1H), 2.06-2.18 (m, 1H),1.89-2.06 (m, 2H), 1.75-1.87 (m, 1H), 1.45-1.63 (m, 1H), 1.22-1.29 (m,1H), 1.11 (d, J = 6.31 Hz, 2H) 680 600 MHz 7.15-7.27 (m, 1H) 7.08 (dd, J= 4.79, 8.60 Hz, 1H), I SFC: DMSO- 6.92 (t, J = 8.75 Hz, 1H), 5.11-5.20(m, 1H), 4.86- Chiralpak d₆ 4.94 (m, 1H), 4.41-4.53 (m, 1H), 4.28-4.41(m, AY-H, 10% 1H), 4.09-4.25 (m, 1H), 4.01 (br d, J = 11.83 Hz, IPA Peak1 1H), 3.77-3.90 (m, 3H), 3.64 (br dd, J = 3.31, 11.87 Hz, 1H),3.44-3.60 (m, 2H), 3.34-3.43 (m, 3H), 3.32 (br s, 2H), 2.97-3.09 (m,3H), 2.75-2.85 (m, 1H), 2.06-2.25 (m, 1H), 1.74-1.84 (m, 1H). 681 600MHz 7.22 (d, J = 9.53 Hz, 1H), 7.18 (t, J = 7.08 Hz, 1H), I SFC: DMSO-6.91 (t, J = 9.33 Hz, 1H), 5.11 (br d, J = 17.36 Hz, Chiralpak d₆ 1H),4.87 (br d, J = 17.05 Hz, 1H), 4.28-4.40 (m, AY-H, 10% 1H), 3.78-3.92(m, 1H), 3.61-3.76 (m, 2H), 3.38- IPA Peak 1 3.53 (m, 2H), 3.26-3.34 (m,3H), 2.95-3.08 (m, 2H), 2.80 (dd, J = 8.29, 12.50 Hz, 1H), 2.02-2.20 (m,2H), 1.75-1.85 (m, 1H), 1.36 (br d, J = 5.76 Hz, 1H), 1.13-1.21 (m, 2H)682 600 MHz 7.14-7.25 (m, 2H), 6.91 (t J = 9.19 Hz, 1H), 4.87 I SFC:DMSO- (q, J = 17.44 Hz, 2H), 4.28-4.40 (m, 1H), 3.97-4.13 Chiralpak d₆(m, 1H), 3.61-3.71 (m, 1H), 3.47-3.60 (m, 1H), AY-H, 10% 3.37-3.46 (m,3H), 2.95-3.11 (m, 2H), 2.75-2.89 IPA Peak 1 (m, 1H), 2.52-1.91 (m, 4H),1.49-1.60 (m, 1H), 1.23-1.29 (m, 1H), 1.11 (d, J = 6.31 Hz, 2H) 683 600MHz 8.43 (br s, 2H), 7.20-7.30 (m, 2H), 6.94-7.05 (m, I SFC: DMSO- 1H),4.78-5.18 (m, 2H), 3.95-4.13 (m, 2H), 3.82- Chiralpak d₆ 3.93 (m, 1H),3.68-3.81 (m, 1H), 3.56-3.68 (m, AY-H, 10% 2H), 3.32-3.48 (m, 2H),2.99-3.37 (m, 1H), 1.98- IPA Peak 1 2.21 (m, 1H), 1.40-1.51-2.0 (m, 1H),1.13-1.30 (m, 7H) 684 600 MHz 7.10-7.26 (m, 2H), 6.90-6.96 (m, 1H),5.11-5.21 I SFC: DMSO- (m, 1H), 4.90-5.00 (m, 1H), 4.41-4.49 (m, 1H),Chiralpak d₆ 4.37 (br d, J= 6.07 Hz, IB), 4.17 (br s, 1H), 3.70- AY-H,10% 3.87 (m, 2H), 3.61 (dt, J = 2.61, 11.50 Hz, 1H), IPA Peak 13.38-3.33 (m, 2H), 3.13-3.20 (m, 1H), 2.99-3.05 (m, 2H), 2.87-2.98 (m,1H), 2.77-2.85 (m, 1H), 2.52-2.55 (m, 1H), 2.29-2.47 (m, 1H), 1.71-1.89(m, 1H), 0.97 (t, J = 7.40 Hz, 1H), 0.81 (dt, J = 1.40, 7.40 Hz, 3H) 685600 MHz 7.22 (br d, J = 9.42 Hz, 1H), 7.16 (br d, J = 4.44 Hz, I SFC:DMSO- 1H), 6.92 (br t, J = 9.19 Hz, 1H), 5.04-5.19 (m, 1H), Chiralpak d₆4.93 (br d, J = 17.44 Hz, 1H), 4.36-4.38 (br m, 1H), AY-H, 10% 3.86-3.95(m, 1H), 3.77-3.86 (m, 2H), 3.53-3.68 IPA Peak 1 (m, 2H), 3.37-3.51 (m,3H), 3.14-3.27 (m, 1H), 2.96-3.08 (m, 2H), 2.77-2.89 (m, 1H), 2.12 (brs, 1H), 1.99 (br s, 1H), 1.75-1.91 (m, 1H), 1.48 (br s, 1H), 0.62 (br s,1H), 0.51 (br s, 1H), 0.42 (br s, 1H), 0.24-0.36 (m, 1H) 686 600 MHz7.14-7.24 (m, 1H), 7.11 (dd, J = 4.79, 8.60 Hz, 1H), I SFC: DMSO-6.85-6.94 (m, 1H), 5.15 (br d, J = 17.52 Hz, 1H), Chiralpak d₆ 5.06 (d,J = 17.44 Hz, 1H), 4.42-4.58 (m, 1H), 3.96- AY-H, 10% 4.04 (m, 1H),3.77-3.94 (m, 2H), 3.59-3.74 (m, IPA Peak 1 2H), 3.44 (br d, J = 9.89Hz, 1H), 3.24-3.41 (m, 2H), 2.97-3.23 (m, 1H), 2.65-2.94 (m, 2H), 2.52-2.56 (m, 1H), 2.07-2.16 (m, 1H), 1.74-1.84 (m, 1H), 1.07-1.19 (m, 2H)687 600 MHz 8.29-8.40 (br s, 2H), 7.21-7.30 (m, 1H), 6.99 (t, I SFC:DMSO- J = 9.33 Hz, 1H), 4.92-5.06 (m, 1H), 3.70-3.88 (m, Chiralpak d₆2H), 3.52-3.70 (m, 6H), 3.33-3.39 (m, 2H), 3.05- AY-H, 10% 3.18 (m, 2H),3.01 (br t, J = 11.99 Hz, 1H), 2.52- IPA Peak 1 2.55 (m, 1H), 1.12-1.41(m, 6H)

Biological Example 1 TRPC6 Calcium Flux Assay

Potency of TRPC6 (Transient receptor potential channel family C6)inhibitors were measured by their inhibition of Calcium influx triggedby OAG (1-Oleoyl-2-acetyl-sn-glycerol. Millipore Sigma.O6754)stimulation on HEK293 cells stablely transfected with human TRPC6 usinga FLIPR tetra system. Cells were grown in a humidified environment at37° C. under 5% CO₂ using the growth medium with the following selectivereagents (Dulbecco's Modified Eagle's Medium (DMEM) high glucose, 10%Fetal Bovine Serum. 1×PSGIu (penicillin-streptomycin glutamine), 1×NEAA(Non-essential amino acid), 1×Na Pyruvate and 200 ug/ml Hygromycin). Forgeneral passage, cells were grown to 70-90% confluency; the media wasremoved, and the cells were gently washed 2 times with calcium andmagnesium free PBS (phosphate-buffered saline). Trypsin (3 mL) wasapplied for 5 minutes at 37° C. The cells were dislodged by rappingflask against base of a hand and 7 mL of growth medium was added todeactivate trypsin and re-suspend cells. The usual splitting schedulewas 1:5 every 2-3 days.

Cells were plated the day before the assay, plating cell density is1.0-1.5×10⁴/25 μl/well in poly-D-lysine (PDL) coated 384-well platesusing either multichannel pipettes or multidrop. These cells were firstincubated with fluorescence dye at room temperature for 90-120 minutesafter they were grown on PDL-coated 384-well black plates overnight (Dyeloading buffer 10 ml example: 9 mL assay buffer, 1 mL, 10×PBX signalenhancer. 10 μL Calcium indicator). The cells were incubated with a doseof compounds for 25 minutes before being stimulated with TRPC6 agonistOAG. The OAG solution was prepared by adding OAG into assay buffer (Caringer solution base: 10 mM HEPES(4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid). 4 mM MgCl₂, 120mM NaCl, 5 mM KCl. pH=7.2 @25° C.)+0.1% BSA+2 mM CaCl₂) to theconcentration of 0.2 mM/2% DMSO, which achieves a final on cellconcentration of 50 uM/0.5% DMSO. 12.5 uL OAG mixture was added and theactivation of the TRPC6 channel was measured by the change ofintracellular Calcium levels on FLIPR terra system.

Data was acquired by measuring the fluorescent peak signal subtractedfrom the background during the 180 second imaging frame. Each data pointis further normalized to 100% of OAG triggered signal vs. buffer. Table16 provides the IC₅₀ for each compound, which data is obtained byplotting peak signal over the compound dose.

TABLE 16 hTRPC6 Potency Ex. # (μM) 1 0.000696 2 0.0032 3 0.00199 40.00167 5 0.00292 6 0.0004002 7 0.0011733 8 0.00028336 9 0.0016133 100.00606 11 0.00179 12 0.000285 13 0.00687 14 0.000377 15 0.00439 160.224 17 0.118 18 0.00785 19 0.000956 20 0.00192 21 0.0006585 22 0.0016223 >3.75 24 0.145 25 0.21 26 0.161 27 0.0735 28 >3.75 29 0.0448 30 1.9431 0.000476 32 0.0472 33 0.0004325 34 0.0689 35 0.000491 36 0.00613 370.00692 38 0.00071978 39 0.000867 40 0.00461 41 0.0184 42 1.94 430.000581 44 0.000952 45 0.00236 46 0.001785 47 0.000686 48 0.002205 490.001095 50 0.000759 51 0.00647 52 0.0242 53 0.00152 54 0.00552 550.00397 56 0.0135 57 0.000784 58 0.000469 59 0.000256 60 0.000261 610.0027 62 0.0603 63 0.000389 64 0.132 65 0.000598 66 0.237 67 0.272 680.0018215 69 0.01471 70 0.002325 71 0.005615 72 0.000448 73 0.0010945 740.38 75 0.0814 76 0.971 77 0.0109 78 0.0707 79 0.00509 80 0.0793 810.557 82 0.000504 83 0.000906 84 0.00127 85 0.00755 86 0.00137 870.000931 88 0.0006428 89 0.368 90 0.068 91 0.0329 92 0.0438 93 0.006853394 0.615 95 >3.75 96 0.134 97 >3.75 98 >3.75 99 >3.75 100 0.06 101 >3.75102 >3.75 103 >3.75 104 0.0618 105 2.48 106 0.0004496 107 0.00788 1080.000433 109 0.0438 110 0.001232 111 0.0007875 112 0.00028147 1130.0002855 114 0.000382 115 0.000446 116 0.00779 117 >3.75 118 0.000855119 0.00194 120 0.00321 121 0.00559 122 0.0299 123 0.252 124 0.000741125 0.000389 126 0.00048 127 0.000492 128 0.04935 129 >3.75 130 0.269131 0.08255 132 0.042 133 0.00698 134 0.00471 135 >3.75 [2] 136 0.013945137 0.0362 138 0.00052 139 0.001905 140 0.132 141 0.0135 142 0.0138 1430.0068625 144 0.000462 145 0.014 146 0.000631 147 0.000433 148 0.0118149 0.00109 150 0.00902 151 0.00606 152 0.0677 153 0.072 154 0.00306 1550.0162 156 0.0617 157 0.000501 158 0.00471 159 0.0164 160 0.0142 1610.133 162 0.257 163 2.84 164 0.253 165 2.06 166 0.56 167 0.0019657 1681.6 169 0.0142 170 0.0259 171 0.544 172 0.00222 173 0.00138 174 0.564175 1.7 176 2.33 177 1.54 178 0.0471 179 0.326 180 0.0149 181 0.000907182 0.314 183 0.655 184 0.143 185 0.003585 186 0.278 187 0.0015905 1880.013025 189 0.0035867 190 0.004015 191 0.13985 192 0.001725 193 0.0485194 0.0142 195 0.000664 196 0.00647 197 0.2555 198 0.07125 199 0.0281200 0.00218 201 0.0439 202 0.002137 203 0.598 204 0.00492 205 0.003 2060.0123 207 0.0496 208 0.0477 209 0.0038675 210 0.0691 211 0.001095 2120.0034975 213 0.00993 214 0.00042 215 0.593 216 0.0114 217 0.0687 2180.00082 219 0.0159 220 0.0009855 221 0.0549 222 0.002045 223 0.0515 2240.158 225 0.00281 226 0.0137 227 0.00032823 228 0.00032 229 0.0422 2300.00049 231 0.737 232 0.00216 233 0.00147 234 0.0269 235 0.15 236 0.0238237 0.223 238 0.185 239 0.562 240 0.0107 241 >3.75 242 0.0735 243 1.97244 >3.75 245 0.0625 246 2.92 247 0.0754 248 0.00507 249 0.00765 2500.0785 251 0.0172 252 0.00876 253 0.406 254 0.0739 255 0.10145 2560.0194 257 0.0524 258 0.0002881 259 1.43 260 0.376 261 >3.75 262 0.28263 0.765 264 0.217 265 2.86 266 15.8 267 >3.75, >50.0 268 >3.75, >50.0269 0.002045 270 0.0515 271 0.158 272 0.00281 273 0.0137 274 0.00032823275 0.00032 276 0.0422 277 0.00049 278 0.737 279 0.00716 280 0.00147 2810.0269 282 0.15 283 0.0238 284 0.223 285 0.185 286 0.562 287 0.0107288 >3.75 289 0.0735 290 1.97 291 >3.75 292 0.0625 293 2.92 294 0.0754295 0.00507 296 0.00765 297 0.0785 298 0.0172 299 0.00876 300 0.406 3010.0739 102 0.10145 303 0.0194 304 0.0524 305 0.0002881 306 1.43 3070.376 308 >3.75 309 0.28 310 0.765 311 0.217 312 2.86 313 15.8314 >3.75, >50.0 315 >3.75, >50.0 316 0.002045 317 1.36 318 0.0377 3190.456 320 0.01205 321 0.00407 322 1.45 323 >3.75 324 >3.75 325 0.743 3262.93 327 1.37 328 >3.75 329 >3.75 330 0.669 331 0.204 332 3.2 333 3.25334 3.54 335 >3.75 336 >3.75 337 >3.75 338 >3.75 339 0.00323 3400.000704 341 0.0258 342 0.0121 343 0.804 344 0.0853 345 0.0015 3460.00139 347 0.00107 348 0.493 349 0.215 350 0.351 351 0.0103 352 0.328353 0.0308 354 0.133 355 0.037 356 0.239 357 0.0245 358 0.00647 3590.238 360 0.0429 361 0.0668 362 0.256 363 0.0313 364 1.02 365 2.96 3660.232 367 0.354 368 0.0992 369 0.00865 370 >50.0 371 6.83 372 14.1 3735.85 374 3.41 375 2.77 376 3.05 377 1.65 378 3.08 379 4.44 380 17 3815.68 382 >50.0 383 0.319 384 16 385 >50.0 386 4.26 387 5.36 388 9.75 3894.58 390 3.57 391 1.82 392 2.24 393 5.05 394 0.732 395 1.12 396 18.2 3971.58 398 0.0874 399 0.0205 400 16.5 401 0.00045573 402 0.00133 4030.000395 404 0.00167 405 0.000708 406 0.000447 407 0.00585 408 0.000924409 0.0010356 410 0.0105 411 0.00268 412 0.322 413 0.221 414 0.0015 4150.274 416 0.00236 417 0.0127 418 0.000584 419 0.128 420 0.0006 4210.0005404 422 0.00235 423 0.151 424 0.000707 425 0.113 426 0.933427 >1.75 428 0.0183 429 >3.75 430 0.88 431 >3.75 432 0.00777 433 >3.75434 >3.75 415 1.16 436 0.0524 437 >3.75 438 0.476 439 0.0367 440 1.34441 0.002235 442 0.000319 443 0.000471 444 0.00442 445 0.0208 446 0.034447 0.119 448 0.123 449 1.16 450 >3.75 451 0.000613 452 0.00117 4530.00151 454 0.00152 455 0.00656 456 0.00844 457 0.0133 458 0.0163 4590.0164 460 0.0242 461 0.0289 462 0.0294 463 0.0339 464 0.0631 465 0.0867466 0.103 467 0.123 468 0.178 469 0.19 470 0.219 471 0.36 472 0.383 4730.398 474 0.411 475 0.62 476 0.763 477 1.03 478 1.05 479 1.2 480 1.2 4812.4 482 2.74 483 2.74 484 >3.75 485 >3.75 486 >1.75 487 >3.75 488 >3.75489 >3.75 490 >3.75 491 >3.75 492 >3.75 493 >3.75 494 0.0126 495 0.0127496 0.0611 497 0.094 498 0.00188 499 0.00258 500 0.005145 501 0.00621502 0.009095 503 0.0256 504 0.0393 505 0.0432 506 0.0766 507 0.102 5080.112 509 0.131 510 0.139 511 0.158 512 0.162 513 0.183 514 0.185 5150.186 516 0.197 517 0.319 518 0.4 519 0.476 520 0.686 521 0.757 5220.762 523 0.988 524 1.49 525 1.78 526 2.85 527 3.01 528 >3.75 529 >1.75530 >3.75 531 >3.75 532 >3.75 533 >3.75 534 >3.75 535 >3.75 536 >3.75537 >1.75 538 >3.75 539 >3.75 540 >3.75 541 >3.75 542 >3.75 543 >3.75544 >3.75 545 >3.75 546 >3.75 547 0.0437 548 0.382 549 0.41 550 >3.75551 0.0061 552 0.00651 553 0.00669 554 0.0109 555 0.0116 556 0.0119 5570.0128 558 0.0161 559 0.0166 560 0.0187 561 0.0198 562 0.0208 563 0.0216564 0.0292 565 0.0322 566 0.0352 567 0.0398 568 0.04805 569 0.0784 5700.0854 571 0.0932 572 0.106 573 0.117 574 0.153 575 0.155 576 0.169 5770.184 578 0.251 579 0.312 580 0.365 581 0.368 582 0.376 583 0.42 5840.546 585 0.579 586 0.747 587 0.765 588 0.811 589 1.01 590 1.44 591 1.59592 1.73 593 2.12 594 >3.75 595 >3.75 596 >3.75 597 >3.75 598 >3.75599 >3.75 600 0.00538 601 0.00556 602 0.00575 603 0.00673 604 0.00778605 0.0079 606 0.00806 607 0.0143 608 0.0183 609 0.0203 610 0.0212 6110.0224 612 0.0224 613 0.0242 614 0.0248 615 0.0285 616 0.0323 617 0.0332618 0.0483 619 0.0574 620 0.0604 621 0.0753 622 0.0789 623 0.089 6240.102 625 0.105 626 0.117 627 0.122 628 0.132 629 0.158 630 0.174 6310.225 632 0.23 633 0.24 634 0.26 635 0.304 636 0.326 637 0.341 638 0.425639 0.657 640 0.809 641 1.28 642 1.65 643 1.82 644 1.91 645 2.3 646 2.31647 3.17 648 3.35 649 >3.75 650 >1.75 651 >3.75 652 >3.75 653 >3.75654 >3.75 655 >3.75 656 >3.75 657 >3.75 658 >3.75 659 >3.75 660 0.005037661 0.279 662 0.283 663 0.294 664 0.555 665 0.584 666 0.687 667 0.745668 0.778 669 0.901 670 1.12 671 1.43 672 1.66 673 >3.75 674 >1.75675 >3.75 676 >3.75 677 0.0881 678 0.0983 679 0.15 680 0.153 681 0.168682 0.259 683 0.29 684 0.524 685 1.16 686 1.57 687 2.08

The foregoing is merely illustrative of the invention and is notintended to limit the invention to the disclosed compounds. Variationsand changes which are obvious to one skilled in the art are intended tobe within the scope and nature of the invention which are defined in theappended claims.

From the foregoing description, one skilled in the art can easilyascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions.

1. A compound or pharmaceutically acceptable salt thereof, according toFormula I:

Wherein p is 0 or 1; when p is 0, then R¹ is hydrogen, C₁-C₆alkyl,halogen or hydroxy; R² is amino or aminoC₁-C₄alkyl; R³ is hydrogen; andR⁴ is hydrogen, C₁-C₆alkyl or phenyl; or when p is 0, then R¹ and R³,taken in combination, form a fused C₃-C₆cycloalkyl ring or a fused 4 to6 member heterocycle ring having 1 or 2 ring heteroatoms independentlyselected from N, O or S, which cycloalkyl or heterocycle is optionallysubstituted with amino; R² is hydrogen, C₁-C₆alkyl or aminoC₁-C₄alkyl;and R⁴ is hydrogen; or when p is 1, then R¹ is NHR^(1a); R^(1a) ishydrogen, C₁-C₄alkyl, C₃-C₇cycloalkyl, hydroxyC₁-C₄alkyl, or 4 to 6member heterocycloalkyl having one ring heteroatom selected from N, O orS; R² is hydrogen, C₁-C₄alkyl, hydroxyC₁-C₄alkyl or C(O)NH₂; R³ ishydrogen, halogen, C₁-C₄alkyl, C₁-C₄alkoxy or hydroxy; and R⁴ ishydrogen, C₁-C₄alkyl or halogen; or when p is 0 or 1, then CR¹R², takenin combination, form a spirocyclic 4 to 6 member heterocycloalkyl; R³ ishydrogen, halogen, C₁-C₄alkyl, C₁-C₄alkoxy, or hydroxy; and R⁴ ishydrogen or halogen; or when p is 1, then R¹ and R³, taken incombination, form a fused 4 to 6 member heterocycle or a fused 3 to 7member carbocycle, which heterocycle comprises a ring nitrogen atom andoptionally 0 or 1 additional ring heteroatoms selected from N, O and S,and which carbocycle is substituted with amino; and R² is hydrogen; andR⁴ is hydrogen, halogen or hydroxy; R⁵ represents 1 or 2 substituentsindependently selected from hydrogen, halogen, hydroxy, amino,C₁-C₆alkyl or C₁-C₆alkoxy; R⁶ is —(CR⁷R⁸)-A; or R⁶ is a 4 to 7 memberlactam which is optionally substituted with one or two substituentsindependently selected from the group consisting of hydroxy, C₁-C₆alkyl,C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl, haloC₁-C₆alkyl,C₁-C₆alkoxy, haloC₁-C₆alkoxy, hydroxyC₁-C₆alkyl, C₁-C₆alkoxyC₁-C₆alkyl,phenyl, 4 to 7 member heterocycle having 1 ring atoms selected from N, Oor S and 0 or 1 additional ring N atoms or 5 or 6 member heteroarylhaving one ring heteroatom selected from N, O or S and 0 or 1 additionalring nitrogen atom, wherein the heteroaryl, heterocycle or phenyl groupis optionally substituted with 0, 1 or 2 C₁-C₆alkyl or halogen; or R⁶ isa partially unsaturated 9 or 10 member bicyclic carbocycle, which isoptionally substituted with 1 or 2 substituents independently selectedfrom halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂ andC(O)NHC₁-C₆alkyl; A is 5 or 6 member heteroaryl, which heteroarylcomprises one ring heteroatom selected from N, O or S and 0, 1 or 2additional ring nitrogen atoms, which heteroaryl is optionallysubstituted with 0, 1, 2, 3 or 4 groups independently selected fromhalogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl,haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)N(R^(A))₂,S(O)₂C₁-C₆alkyl, phenyl or 5 or 6 member heteroaryl having one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, wherein the optional heteroaryl or phenyl substituent isfurther substituted with 0, 1 or 2 C₁-C₆alkyl; or A is phenylsubstituted with 1, 2 or 3 substituents independently selected fromhalogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, haloC₁-C₆alkyl,cyanoC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, cyanoC₁-C₆ alkoxy,S(O)C₁-C₆alkyl, S(O)₂NH₂, S(O)₂NHC₁-C₆alkyl, S(O)₂N(C₁-C₆alkyl)₂,C(O)NH₂, C(O)NHC₁-C₆alkyl, C(O)N(C₁-C₆alkyl)₂, hydroxy, cyano, or 5 or 6member heteroaryl having one ring heteroatom selected from N, O or S and0, 1 or 2 additional ring nitrogen atoms which heteroaryl is furthersubstituted with 0, 1 or 2 C₁-C₆alkyl; or A is C(O)OR⁹ or C(O)NR⁹R¹⁰; orA is optionally substituted 9 or 10 member aromatic or partiallyunsaturated bicyclyl having 0, 1 or 2 ring nitrogen atoms and 0 or 1additional ring heteroatoms selected from N, O or S, which bicyclyl issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl,C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂,C(O)OH or C(O)NHC₁-C₆alkyl; R^(A) is independently selected at eachoccurrence from hydrogen or C₁-C₄alkyl; or N(R^(A))₂, taken incombination, forms a 4 to 7 member azacycle which is optionallysubstituted with 0, 1, or 2 C₁-C₄alkyl; R⁷ is hydrogen, C₁-C₄alkyl oramino; R⁸ is hydrogen or C₁-C₄alkyl; or CR⁷R⁸, taken in combination forma 3 to 6 member cycloalkandiyl group; R⁹ is hydrogen, C₁-C₆alkyl,C₃-C₆cycloalkyl, hydroxyC₁-C₆alkyl, C₁-C₄alkoxyC₁-C₆alkyl,haloC₁-C₆alkyl, cyano C₁-C₆alkyl or —(CH₂)_(r)R^(9A) wherein r is 0 or 1and R^(9A) is phenyl, 4 to 7 member heterocycle having one ringheteroatoms selected from N, O or S, which ring sulfur may be optionallyoxidized, and 0 or 1 additional ring N atoms or 5 or 6 member heteroarylhaving one ring heteroatom selected from N, O or S and 0, 1, or 2additional ring N atoms, which phenyl, heterocycle or heteroaryl isoptionally substituted with 0, 1 or 2 halogen, C₁-C₄alkyl orC(O)C₁-C₄alkyl; R¹⁰ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,halo C₁-C₆alkyl, C₃-C₇cycloalkyl or saturated, partially unsaturated oraromatic 5 or 6 member heterocycle having 1 or 2 ring heteroatomsindependently selected from N, O and S, which sulfur is optionallyoxidized, and which heterocycle is optionally substituted with 1 or 2substituents independently selected from C₁-C₆alkyl and halogen, whichheterocycle has 1 or 2 ring hetero atoms selected from N, O or S, whichsulfur may be optionally oxidized, and wherein each alkyl or cycloalkylis optionally substituted with cyano, halogen, hydroxy, C₁-C₆alkoxy,S(O)_(q), C₁-C₆alkyl, 4 to 6 member heterocycle having 1 or 2 ringheteroatoms selected from N, O or S or 5 or 6 member heteroaryl having 1ring heteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms and where each heterocycle or heteroaryl is optionallysubstituted with 0, 1, or 2 C₁-C₄alkyl; or NR⁹R¹⁰, taken in combination,form a monocyclic or bicyclic 4 to 10 member saturated or partiallyunsaturated heterocycle having one or two ring nitrogen atoms and 0 or 1additional ring heteroatom selected from N, O or S, which ring sulfurmay be optionally oxidized, which heterocycle is optionally substitutedwith 0, 1 or 2 substitutents selected from halogen, oxo, hydroxy, cyano,C₁-C₆alkyl, C₃-C₆cycloalkyl, haloC₁-C₆alkyl, hydroxyC₁-C₆alkyl,cyanoC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C₁-C₆alkoxyC₁-C₄alkyl,S(O)_(q)C₁-C₆alkyl, C₁-C₆alkylS(O)_(q)C₁-C₆alkyl CO₂H, C(O)C₁-C₆alkyl,C(O)OC₁-C₆alkyl, C(O)C₃-C₆cycloalkyl, N(R¹⁵)C(O)C₁-C₆alkyl orC(O)N(R¹⁵)₂, phenyl, 4 to 6 member heterocycle having 1 or 2 ringheteroatoms selected from N, O or S or a 5 or 6 member heteroaryl having1 ring heteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms and where each heterocycle or heteroaryl is optionallysubstituted with 0, 1, or 2 C₁-C₄alkyl; q is 0, 1 or 2; Z¹ is N or CR¹¹;Z² is N or CR²; Z³ is N or CR³; Z⁴ is N or CR¹⁴, Z⁵ and Z⁶ are eachindependently N or C; wherein 0, 1 or 2 of Z¹, Z², Z³, Z⁴, Z⁵ and Z⁶ areN; each of R¹¹, R¹², R¹³ and R¹⁴ is independently selected from thegroup consisting of hydrogen, halogen, C₁-C₆alkyl, C₂-C₆alkenyl,C₂-C₆alkynyl, C₁-C₆alkoxy, haloC₁-C₆alkyl, haloC₁-C₆alkoxy,C₃-C₇cycloalkyl, cyano, SO₂C₁-C₆alkyl, phenyl, and saturated, partiallyunsaturated or aromatic 5 or 6 member heterocycle having 1 or 2 ringheteroatoms independently selected from N, O and S, which heterocycle isoptionally substituted with 1 or 2 substituents independently selectedfrom C₁-C₆alkyl and halogen; and R¹⁵ is selected at each occurrence fromhydrogen or C₁-C₄alkyl or N(R¹⁵)₂ taken in combination form a 4 to 7member azacycle optionally substituted with 0, 1 or 2 C₁-C₄alkyl; withthe proviso that compounds of Formula I do not include1-[7-fluoro-6-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-1H-benzimidazol-2-yl]-3-piperidinamine.2. A compound or pharmaceutically acceptable salt thereof, according toFormula I:

Wherein p is 0 or 1; when p is 0, then R¹ is hydrogen, C₁-C₆alkyl,halogen or hydroxy; R² is amino or aminoC₁-C₄alkyl; R³ is hydrogen; andR⁴ is hydrogen, C₁-C₆alkyl or phenyl; or when p is 0, then R¹ and R³,taken in combination, form a fused C₃-C₆cycloalkyl ring or a fused 4 to6 member heterocycle ring having 1 or 2 ring heteroatoms independentlyselected from N, O or S, which cycloalkyl or heterocycle is optionallysubstituted with amino; R² is hydrogen, C₁-C₆alkyl or aminoC₁-C₄alkyl;and R⁴ is hydrogen; or when p is 1, then R¹ is NHR^(1a); R^(La) ishydrogen, C₁-C₄alkyl, C₃-C₇cycloalkyl, hydroxyC₁-C₄alkyl, or 4 to 6member heterocycloalkyl having one ring heteroatom selected from N, O orS; R² is hydrogen, C₁-C₄alkyl, hydroxyC₁-C₄alkyl or C(O)NH₂; R³ ishydrogen, halogen, C₁-C₄alkyl, C₁-C₄alkoxy or hydroxy; and R⁴ ishydrogen, C₁-C₄alkyl or halogen; or when p is 0 or 1, thenC(NHR^(1a))R², taken in combination, form a spirocyclic 4 to 6 memberheterocycloalkyl; R³ is hydrogen, halogen C₁-C₄alkyl, C₁-C₄alkoxy, orhydroxy; and R⁴ is hydrogen or halogen; or when p is 1, then R¹ and R³,taken in combination, form a fused 4 to 6 member heterocycle or a fused3 to 7 member carbocycle, which heterocycle comprises a ring nitrogenatom and optionally 0 or 1 additional ring heteroatoms selected from N,O and S, and which carbocycle is substituted with amino; and R² ishydrogen; and R⁴ is hydrogen, halogen or hydroxy; R⁵ represents 1 or 2substituents independently selected from hydrogen, halogen, hydroxy,amino, C₁-C₆alkyl or C₁-C₆alkoxy; R⁶ is —(CR⁷R⁸)-A; or R⁶ is a 4 to 7member lactam which is optionally substituted with one or twosubstituents independently selected from the group consisting ofhydroxy, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, haloC₁-C₆alkyl,C₁-C₆alkoxy, haloC₁-C₆alkoxy, hydroxyC₁-C₆alkyl, C₁-C₆alkoxyC₁-C₆alkyl,phenyl or 5 or 6 member heteroaryl having one ring heteroatom selectedfrom N, O or S and 0 or 1 additional ring nitrogen atom, wherein theheteroaryl or phenyl group is optionally substituted with 0, 1 or 2C₁-C₆alkyl or halogen; or R⁶ is a partially unsaturated 9 or 10 memberbicyclic carbocycle, which is optionally substituted with 1 or 2substituents independently selected from halogen, cyano, C₁-C₆alkyl,C₂-C₆alkenyl, C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy,haloC₁-C₆alkoxy, C(O)NH₂ and C(O)NHC₁-C₆alkyl; A is 5 or 6 memberheteroaryl, which heteroaryl comprises one ring heteroatom selected fromN, O or S and 0, 1 or 2 additional ring nitrogen atoms, which heteroarylis optionally substituted with 0, 1, 2, 3 or 4 groups independentlyselected from halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl,haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂, C(O)NHC₁-C₆alkyl,phenyl or 5 or 6 member heteroaryl having one ring heteroatom selectedfrom N, O or S and 0, 1 or 2 additional ring nitrogen atoms, wherein theoptional heteroaryl or phenyl substituent is further substituted with 0,1 or 2 C₁-C₆alkyl; or A is phenyl substituted with 1, 2 or 3substituents independently selected from halogen, C₁-C₆alkyl,C₂-C₆alkenyl, C₂-C₆alkynyl, haloC₁-C₆alkyl, cyanoC₁-C₆alkyl,C₁-C₆alkoxy, haloC₁-C₆alkoxy, cyanoC₁-C₆ alkoxy, S(O)_(q)C₁-C₆alkyl,S(O)₂NH₂, S(O)₂NHC₁-C₆alkyl, S(O)₂N(C₁-C₆alkyl)₂, C(O)NH₂,C(O)NHC₁-C₆alkyl, C(O)N(C₁-C₆alkyl)₂, hydroxy, cyano, or 5 or 6 memberheteroaryl having one ring heteroatom selected from N, O or S and 0, 1or 2 additional ring nitrogen atoms which heteroaryl is furthersubstituted with 0, 1 or 2 C₁-C₆alkyl; or A is C(O)OR⁹ or C(O)NR⁹R¹⁰; orA is optionally substituted 9 or 10 member aromatic or partiallyunsaturated bicyclyl having 0, 1 or 2 ring nitrogen atoms and 0 or 1additional ring heteroatoms selected from N, O or S, which bicyclyl issubstituted with 0, 1 or 2 substituents independently selected from thegroup consisting of halogen, cyano, C₁-C₆alkyl, C₂-C₆alkenyl,C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, C(O)NH₂,C(O)OH or C(O)NHC₁-C₆alkyl; R⁷ is hydrogen, C₁-C₄alkyl or amino; R⁸ ishydrogen or C₁-C₄alkyl; or CR⁷R⁸, taken in combination form a 3 to 6member cycloalkandiyl group; R⁹ is hydrogen, C₁-C₆alkyl,hydroxyC₁-C₆alkyl, haloC₁-C₆alkyl or cyano C₁-C₆alkyl; R^(L0) ishydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, halo C₁-C₆alkyl,C₃-C₇cycloalkyl or 4 to 7 member heterocycle, which heterocycle has 1 or2 ring hetero atoms selected from N, O or S, which sulfur may beoptionally oxidized, and wherein each alkyl or cycloalkyl is optionallysubstituted with cyano, halogen, hydroxy, C₁-C₆alkoxy, S(O)_(q),C₁-C₆alkyl, 4 to 6 member heterocycle having 1 or 2 ring heteroatomsselected from N, O or S or 5 or 6 member heteroaryl having 1 ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms; or NR⁹R¹⁰, taken in combination, form a monocyclic orbicyclic 4 to 9 member heterocycle having one ring nitrogen atom and 0or 1 additional ring heteroatom selected from N, O or S, which ringsulfur may be optionally oxidized, which heterocycle is optionallysubstituted with 0, 1 or 2 substitutents selected from halogen, oxo,hydroxy, cyano, C₁-C₆alkyl, halo C₁-C₆alkyl, hydroxyC₁-C₆alkyl,C₁-C₆alkoxy, S(O)_(q)C₁-C₆alkyl, CO₂H, C(O)C₁-C₆alkyl, or C(O)NH₂; q is0, 1 or 2; Z¹ is N or CR¹¹; Z² is N or CR²; Z³ is N or CR¹³; Z⁴ is N orCR¹⁴, Z⁵ and Z⁶ are each independently N or C; wherein 0, 1 or 2 of Z¹,Z², Z³, Z⁴, Z⁵ and Z⁶ are N; each of R¹¹, R¹², R¹³ and R¹⁴ isindependently selected from the group consisting of hydrogen, halogen,C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆alkoxy, haloC₁-C₆alkyl,haloC₁-C₆alkoxy, C₃-C₇cycloalkyl, cyano, SO₂C₁-C₆alkyl, phenyl, andsaturated, partially unsaturated or aromatic 5 or 6 member heterocyclehaving 1 or 2 ring heteroatoms independently selected from N, O and S,which heterocycle is optionally substituted with 1 or 2 substituentsindependently selected from C₁-C₆alkyl and halogen; and with the provisothat compounds of Formula I do not include1-[7-fluoro-6-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-1H-benzimidazol-2-yl]-3-piperidinamine.3. The compound or pharmaceutical acceptable salt thereof of claim 2,wherein p is 0; R¹ and R³, taken in combination, form a fusedC₃-C₆cycloalkyl ring or a fused 4 to 6 member azacycle ring, whichcycloalkyl or azacycle is optionally substituted with amino; and R² andR⁴ are hydrogen.
 4. The compound or pharmaceutically acceptable saltthereof of claim 2, wherein p is 1, R¹ is NHR^(1a); R^(1a) is hydrogen,C₁-C₄alkyl, C₃-C₇cycloalkyl or 4 to 6 member heterocycloalkyl having onering heteroatom selected from N, O or S; R² is hydrogen or C₁-C₄alkyl;R³ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₄alkoxy, or hydroxy; and R⁴ ishydrogen, halogen or C₁-C₄alkyl
 5. The compound or pharmaceuticallyacceptable salt thereof of claim 4, wherein R¹ is NHR^(1a); R^(1a) ishydrogen, methyl, ethyl, propyl, isopropyl or cyclopropyl; R² ishydrogen or methyl; R³ is hydrogen, halogen, methyl, ethyl, methoxy,ethoxy, or hydroxy; and R⁴ is hydrogen, halogen, methyl or ethyl.
 6. Thecompound or pharmaceutically acceptable salt thereof of claim 4, whereinR¹ is NH₂; R² is hydrogen; R³ is hydrogen, fluorine, methyl, or hydroxy;and R⁴ is hydrogen, fluorine or methyl.
 7. The compound orpharmaceutically acceptable salt thereof of claim 2, wherein R⁶ is—(CR⁷R⁸)-A.
 8. The compound or pharmaceutically acceptable salt thereofof claim 7, wherein R⁷ is hydrogen or methyl; and R⁸ is hydrogen.
 9. Thecompound or pharmaceutically acceptable salt thereof of claim 7, whereinA is 5 or 6 member heteroaryl, which heteroaryl comprises one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, which heteroaryl is optionally substituted with 0, 1, or2 groups independently selected from halogen, cyano, C₁-C₆alkyl,C₂-C₆alkenyl, C₂-C₆alkynyl, haloC₁-C₆alkyl, C₁-C₆alkoxy,haloC₁-C₆alkoxy, C(O)NH₂, C(O)NHC₁-C₆alkyl, phenyl or 5 or 6 memberheteroaryl having one ring heteroatom selected from N, O or S and 0, 1or 2 additional ring nitrogen atoms, wherein the optional heteroaryl orphenyl substituent is further substituted with 0, 1 or 2 C₁-C₆alkyl. 10.The compound or pharmaceutically acceptable salt thereof of claim 9,wherein A is pyridin-2-yl, pyridin-3-yl, pyrimidin-2-yl, orpyrazin-2-yl, each of which is substituted with 1 to 3 groupsindependently selected from the group consisting of halogen, cyano,C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkoxy, C(O)NH₂,C(O)NHC₁-C₄alkyl, phenyl or 5 member heteroaryl having one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms, wherein the optional heteroaryl or phenyl substituent isfurther substituted with 0, 1 or 2 C₁-C₆alkyl.
 11. The compound orpharmaceutically acceptable salt thereof of claim 7, wherein A is phenylsubstituted with one substituent selected from the group consisting ofhalogen, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkoxy,hydroxy, cyano, or 5 member heteroaryl having one ring heteroatomselected from N, O or S and 0, 1 or 2 additional ring nitrogen atoms,and wherein the phenyl group is further optionally substituted withhalogen, C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkyl or haloC₁-C₄alkoxy. 12.The compound or pharmaceutically acceptable salt thereof of claim 7,wherein A is C(O)NR⁹R¹⁰; R⁹ is hydrogen, or C₁-C₄alkyl; R¹⁰ isC₁-C₄alkyl, haloC₁-C₄alkyl, C₃-C₇cycloalkyl or 4 to 7 memberheterocycle, which heterocycle has 1 or 2 ring hetero atoms selectedfrom N, O or S, which sulfur may be optionally oxidized, and whereineach alkyl or cycloalkyl is optionally substituted with cyano, halogen,hydroxy, C₁-C₆alkoxy, S(O)_(q), C₁-C₆alkyl; or NR⁹R¹⁰, taken incombination, form a monocyclic or bicyclic 4 to 9 member azacycle havingone ring nitrogen atom and 0 or 1 additional ring heteroatom selectedfrom N, O or S, which ring sulfur may be optionally oxidized, whichazacycle is optionally substituted with 0, 1 or 2 substitutents selectedfrom halogen, oxo, hydroxy, cyano, C₁-C₆alkyl, halo C₁-C₆alkyl,hydroxyC₁-C₆alkyl, C₁-C₆alkoxy, S(O)₂C₁-C₆alkyl, CO₂H, C(O)C₁-C₆alkyl,or C(O)NH₂.
 13. The compound or pharmaceutically acceptable salt thereofof claim 12, wherein R⁹ is hydrogen, methyl or ethyl; and R¹⁰ isC₁-C₄alkyl or haloC₁-C₄alkyl wherein each alkyl is optionallysubstituted with cyano, halogen, hydroxy, C₁-C₆alkoxy or S(O)C₁-C₆alkyl.14. The compound or pharmaceutically acceptable salt thereof of claim12, wherein NR⁹R¹⁰, taken in combination, form a 4 to 6 membermonocyclic azacycle or a 7 to 9 member bicyclic azacycle, each of whichhaving one ring nitrogen atom and 0 or 1 additional ring heteroatomselected from N, O or S, which ring sulfur may be optionally oxidized,wherein each azacycle is optionally substituted with 0, 1 or 2substitutents selected from halogen, oxo, hydroxy, cyano, C₁-C₆alkyl,halo C₁-C₆alkyl, hydroxyC₁-C₆alkyl, C₁-C₆alkoxy, S(O)₂C₁-C₆alkyl, CO₂H,C(O)C₁-C₆alkyl, or C(O)NH₂.
 15. The compound pharmaceutically acceptablesalt thereof of claim 3, wherein Z¹ is CR¹¹; Z² is CR¹²; Z³ is CR¹³; Z⁴is N or CR¹⁴, Z⁵ and Z⁶ are each C; R¹¹ is hydrogen, halogen, cyano orC₁-C₄alkyl; R¹² and R¹³ are each independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl,C₁-C₄alkoxy, haloC₁-C₄alkoxy C₃-C₆cycloalkyl or 5 member saturated,partially unsaturated or aromatic 5 or 6 member heterocycle having 1 or2 ring heteroatoms independently selected from N, O and S; and R¹⁴ ishydrogen, halogen, cyano or C₁-C₄alkyl.
 16. The compound orpharmaceutically acceptable salt thereof of claim 2 which is a compoundof Formula III:

Wherein X¹ is CR¹⁶ or N; X² is CR¹⁷ or N; X³ is CR¹⁸ or N; Z⁴ is N orCR¹⁴; R¹ is NHR^(1a); R^(1a) is hydrogen or C₁-C₄alkyl; R² is hydrogenor C₁-C₄alkyl; R³ is hydrogen or halogen; R⁴ is hydrogen or halogen; R⁷is hydrogen, methyl or ethyl; R¹¹ is hydrogen, halogen, cyano orC₁-C₄alkyl; R¹² and R¹³ are each independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl,C₁-C₄alkoxy, or haloC₁-C₄alkoxy; R¹⁴ is hydrogen, halogen, cyano orC₁-C₄alkyl; R¹⁵ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkyl, haloC₁-C₄alkoxy, C(O)NH₂, C(O)NH(C₁-C₄alkyl) or 5 memberheteroaryl having one ring heteroatom selected from N, O or S and 0, 1or 2 additional ring nitrogen atoms; R¹⁶ is hydrogen, halogen, cyano,C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkyl or haloC₁-C₄alkoxy; R¹⁷ ishydrogen or halogen; and R¹⁸ is hydrogen, halogen, cyano, C₁-C₄alkyl,C₁-C₄alkoxy, haloC₁-C₄alkyl or haloC₁-C₄alkoxy, wherein at least one ofR¹⁵, R¹⁶, R¹⁷ or R¹⁸ is not hydrogen.
 17. The compound orpharmaceutically acceptable salt thereof of claim 2 which is a compoundof Formula VI:

Wherein R^(1a) is hydrogen or C₁-C₄alkyl; R³ is hydrogen or halogen; R⁴is hydrogen or halogen; R⁷ is hydrogen, methyl or ethyl; R¹¹ ishydrogen, halogen, cyano or C₁-C₄alkyl; R¹² and R¹³ are eachindependently selected from the group consisting of hydrogen, halogen,cyano, C₁-C₄alkyl, haloC₁-C₄alkyl, C₁-C₄alkoxy, or haloC₁-C₄alkoxy; R¹⁴is hydrogen, halogen, cyano or C₁-C₄alkyl; R¹⁵ is hydrogen, halogen,cyano, C₁-C₄alkyl, C₁-C₄alkoxy, haloC₁-C₄alkyl, haloC₁-C₄alkoxy,C(O)NH₂, C(O)NH(C₁-C₄alkyl) or 5 member heteroaryl having one ringheteroatom selected from N, O or S and 0, 1 or 2 additional ringnitrogen atoms; R¹⁶ is hydrogen, halogen, cyano, C₁-C₄alkyl,C₁-C₄alkoxy, haloC₁-C₄alkyl or haloC₁-C₄alkoxy; R¹⁷ is hydrogen orhalogen; and R¹⁸ is hydrogen, halogen, cyano, C₁-C₄alkyl, C₁-C₄alkoxy,haloC₁-C₄alkyl or haloC₁-C₄alkoxy, wherein at least one of R¹⁵, R¹⁶, R¹⁷or R¹⁸ is not hydrogen.
 18. The compound or pharmaceutically acceptablesalt thereof of claim 2 which is a compound of Formula VII:

Wherein R^(1a) is hydrogen or C₁-C₄alkyl; R³ is hydrogen or halogen; R⁴is hydrogen or halogen; R⁷ is hydrogen, methyl or ethyl; R⁹ is hydrogen,methyl or ethyl; R^(L0) is C₁-C₄alkyl or haloC₁-C₄alkyl wherein eachalkyl is optionally substituted with cyano, halogen, hydroxy,C₁-C₆alkoxy or S(O)C₁-C₆alkyl; or NR⁹R¹⁰, taken in combination, form a 4to 6 member monocyclic azacycle or a 7 to 9 member bicyclic azacycle,each of which having one ring nitrogen atom and 0 or 1 additional ringheteroatom selected from N, O or S, which ring sulfur may be optionallyoxidized, wherein each azacycle is optionally substituted with 0, 1 or 2substitutents selected from halogen, oxo, hydroxy, cyano, C₁-C₆alkyl,halo C₁-C₆alkyl, hydroxyC₁-C₆alkyl, C₁-C₆alkoxy, S(O)₂C₁-C₆alkyl, CO₂H,C(O)C₁-C₆alkyl, or C(O)NH₂; R¹¹ is hydrogen, halogen, cyano orC₁-C₄alkyl; R¹² and R¹³ are each independently selected from the groupconsisting of hydrogen, halogen, cyano, C₁-C₄alkyl, haloC₁-C₄alkyl,C₁-C₄alkoxy, or haloC₁-C₄alkoxy; and R¹⁴ is hydrogen, halogen, cyano orC₁-C₄alkyl.
 19. The compound or pharmaceutically acceptable salt thereofof claim 16, wherein R¹¹ is hydrogen.
 20. The compound orpharmaceutically acceptable salt thereof of claim 16, wherein R^(1a) ishydrogen or methyl; R³ is hydrogen or fluorine; and R⁴ is hydrogen orfluorine.
 21. (canceled)
 22. A compound or pharmaceutically acceptablesalt thereof, which compound is selected from the group, consisting of6-((2-((3R,4S)-3-amino-4-fluoropiperidin-1-yl)-6-chloro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazole-4-carbonitrile;(3R,4R)-1-(4,6-difluoro-1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine;6-((2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-4,6-difluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrilehydrochloride;(R)-6-((2-(3-amino-4,4-difluoropiperidin-1-yl)-6-fluoro-1H-benzo[d]imidazol-1-yl)methyl)nicotinonitrile;6-((2-((3R,4R)-3-amino-4-fluoro-1-piperidinyl)-4-methoxy-1H-benzimidazol-1-yl)methyl)-3-pyridinecarbonitrile;(2-((3R,4R)-3-amino-4-fluoropiperidin-1-yl)-1-((5-chloropyrimidin-2-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile;(3R,4R)-4-fluoro-1-(1-((5-fluoropyrimidin-2-yl)methyl)-1H-benzo[d]imidazol-2-yl)piperidin-3-amine;and(3R,4R)-1-(1-((5-chloropyrimidin-2-yl)methyl)-6-fluoro-1H-benzo[d]imidazol-2-yl)-4-fluoropiperidin-3-amine.23. The compound or pharmaceutically acceptable salt thereof of claim 2in a form of a pharmaceutically acceptable salt.
 24. A pharmaceuticalcomposition comprising a pharmaceutically acceptable excipient, carrieror adjuvant and at least one compound of claim
 2. 25. A method oftreating a disease or disorder mediated by TRPC6 in a mammal whichmethod comprises administering to the mammal a therapeutically effectiveamount of at least one compound of claim 2, or a pharmaceutical saltthereof or a pharmaceutical composition thereof.
 26. The method of claim25, wherein the disease or disorder mediated by TRPC6 is selected fromthe group consisting of nephrotic syndrome, minimal change disease,focal segmental glomerulosclerosis, collapsing glomerulopathy,membranous nephropathy, membranoproliferative glomerulonephritis, IGAnephropathy, acute renal failure, chronic renal failure, diabeticnephropathy, sepsis, pulmonary hypertension, acute lung disorder, acuterespiratory distress syndrome (ARDS), heart failure, stroke, malignanttumor, and muscular dystrophy.
 27. A method for modulating TRPC6activity in a mammal which method comprises administering to the mammalan amount of at least one compound of claim 2 or a pharmaceutical saltthereof or a pharmaceutical composition thereof to modulate TRPC6activity in the mammal.
 28. (canceled)
 29. (canceled)